Home Protein Tyrosine Kinase c-Met remmer PF-02341066 (Crizotinib)

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PF-02341066 (Crizotinib) ALK/c-Met/ROS1 remmer

Cat.nr.S1068

Crizotinib is een krachtige remmer van c-Met en ALK met IC50 van respectievelijk 11 nM en 24 nM in celgebaseerde assays. Het is ook een krachtige ROS1 remmer met een Ki-waarde van minder dan 0,025 nM. Crizotinib induceert autofagie door remming van de STAT3-route in meerdere longkankercellijnen.
PF-02341066 (Crizotinib) c-Met remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 450.34

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Kwaliteitscontrole

Batch: Zuiverheid: 99.92%
99.92

Celkweek, behandeling & werkzame concentratie

Cellijnen Assaytype Concentratie Incubatietijd Formulering Activiteitsbeschrijving PMID
SU-DHL1 Cytotoxic Assay Cytotoxicity against human SU-DHL1 cells expressing ALK coexpressing NPM with IC50 of 0.01 μM 21572589
BAF3 Cytotoxic Assay 48 h DMSO Cytotoxicity against mouse BAF3 cells expressing ALK F1174L mutant coexpressing EML4 with IC50 of 0.62 μM 21572589
BAF3 Cytotoxic Assay 48 h DMSO Cytotoxicity against mouse BAF3 cells expressing ALK L1196M mutant coexpressing EML4 with IC50 of 2.2 μM 21572589
BAF3 Cytotoxic Assay 48 h DMSO Cytotoxicity against mouse BAF3 cells expressing EML4-ALK with IC50 of 0.28 μM 21572589
Kelly Cytotoxic Assay DMSO Cytotoxicity against human Kelly cells expressing ALK F1174L mutant with IC50 of 0.42 μM 21572589
SH-SY5Y Cytotoxic Assay DMSO Cytotoxicity against human SH-SY5Y cells expressing ALK F1174L mutant with IC50 of 0.53 μM 21572589
SMS-KCN Cytotoxic Assay DMSO Cytotoxicity against human SMS-KCN cells expressing ALK R1275Q mutant with IC50 of 0.91 μM 21572589
BAF3 Cytotoxic Assay 48 h DMSO Cytotoxicity against mouse BAF3 cells expressing Tel-ALK with IC50 of 0.19 μM 21572589
3T3 Function Assay 1 h DMSO Inhibition of RON assessed as growth factor-induced autophosphorylation with IC50 of 0.08 μM 21812414
3T3-E Function Assay 1 h DMSO Inhibition of TIE2 assessed growth factor-induced autophosphorylation with IC50 of 0.448 μM 21812414
A549 Kinase Assay 1 h DMSO Inhibition of human recombinant c-MET kinase expressed assessed as inhibition of HGF-induced autophosphorylation with IC50 of 0.008 μM 21812414
BAF3-BCL Function Assay 1 h DMSO Inhibition of ABL assessed as growth factor-induced autophosphorylation with IC50 of 1.159 μM 21812414
HEK293 Function Assay 1 h DMSO Inhibition of AXL assessed as growth factor-induced autophosphorylation with IC50 of 0.294 μM 21812414
HEK293 Function Assay 1 h DMSO Inhibition of IR assessed as growth factor-induced autophosphorylation with IC50 of 2.887 μM 21812414
Jurkat Function Assay 1 h DMSO Inhibition of LCK assessed as growth factor-induced autophosphorylation with IC50 of 2.741 μM 21812414
KARPAS299 Kinase Assay 1 h DMSO Inhibition of ALK assessed as growth factor-induced autophosphorylation with IC50 of 0.02 μM 21812414
PAE Function Assay 1 h DMSO Inhibition of TRKB assessed as growth factor-induced autophosphorylation with IC50 of 0.399 μM 21812414
PAE Function Assay 1 h DMSO Inhibition of TRKA assessed as growth factor-induced autophosphorylation with IC50 of 0.58 μM 21812414
BAF3 Function Assay 2-3 d DMSO Inhibition of TEL-fused insulin receptor expressed with IC50 of 1.643 μM 23742252
BAF3 Function Assay 2-3 d DMSO Inhibition of NPM-fused ALK (unknown origin) expressed in mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay with IC50 of 0.1508 μM 23742252
BAF3 Function Assay 2-3 d DMSO Cytotoxicity against mouse BAF3 cells after 2 to 3 days by luciferase reporter gene assay with IC50 of 3.479 μM 23742252
KARPAS299 Cytotoxic Assay 2-3 d DMSO IC50=0.0642 μM 23742252
EBC1 Growth Inhibition Assay 72 h DMSO IC50=0.023 μM 23993328
HCT116 Growth Inhibition Assay 72 h DMSO IC50=14.82 μM 23993328
MCF7 Growth Inhibition Assay 72 h DMSO IC50=9.58 μM 23993328
MDA-MB-231 Growth Inhibition Assay 72 h DMSO IC50=10.8 μM 23993328
MKN45 Growth Inhibition Assay 72 h DMSO IC50=0.013 μM 23993328
NCI-H441 Growth Inhibition Assay 72 h DMSO IC50=17.25 μM 23993328
NCI-H661 Growth Inhibition Assay 72 h DMSO IC50=11.47 μM 23993328
SK-MEL-28 Growth Inhibition Assay 72 h DMSO IC50=10.97 μM 23993328
SKOV3 Growth Inhibition Assay 72 h DMSO IC50=12.85 μM 23993328
SNU5 Growth Inhibition Assay 72 h DMSO IC50=0.016 μM 23993328
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells expressing elevated levels of constitutively active c-Met after 72 hrs by SRB assay, IC50 = 0.053 μM. 22863529
Function assay KARPAS299 72 hrs Inhibition of ALK-fusion driven cell proliferation in human KARPAS299 cells after 72 hrs by CellTiter Glo assay, IC50 = 0.062 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human wild type EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA, IC50 = 0.08 μM. 24432909
Function assay NCI-H3122 72 hrs Inhibition of ALK-fusion driven cell proliferation in human NCI-H3122 cells after 72 hrs by CellTiter Glo assay, IC50 = 0.108 μM. 24432909
Function assay NCI-H2228 72 hrs Inhibition of ALK-fusion driven cell proliferation in human NCI-H2228 cells after 72 hrs by CellTiter Glo assay, IC50 = 0.118 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.165 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.478 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.605 μM. 24432909
Function assay NCI-H3122 72 hrs Inhibition of ALK-fusion driven cell proliferation in human NCI-H3122 cells harboring ALK G1269A mutant after 72 hrs by CellTiter Glo assay, IC50 = 0.623 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.626 μM. 24432909
Function assay NCI-H3122 72 hrs Inhibition of ALK-fusion driven cell proliferation in human NCI-H3122 cells harboring ALK L1196M mutant after 72 hrs by CellTiter Glo assay, IC50 = 0.838 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.843 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 1.026 μM. 24432909
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 3.039 μM. 24432909
Function assay BAF3 72 hrs Inhibition of NPM/ALK (unknown origin) transfected in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by [3H]-thymidine incorporation assay, IC50 = 0.051 μM. 24468632
Function assay BAF3 72 hrs Inhibition of NPM/ALK (unknown origin) transfected in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by [3H]-thymidine incorporation assay, IC50 = 0.051 μM. 24468632
Function assay BAF3 72 hrs Inhibition of NPM/ALK L1196M mutant (unknown origin) transfected in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by [3H]-thymidine incorporation assay, IC50 = 0.26 μM. 24468632
Cytotoxicity assay BAF3 72 hrs Cytotoxicity against mouse BAF3 cells assessed as growth inhibition after 72 hrs by [3H]-thymidine incorporation assay, IC50 = 0.98 μM. 24468632
Antiproliferative assay NIH/3T3 72 hrs Antiproliferative activity against crizotinib-resistant mouse NIH/3T3 cells harboring EML4-ALK variant 1 after 72 hrs by MTT assay, IC50 = 0.0954 μM. 24785465
Antiproliferative assay SUP-M2 72 hrs Antiproliferative activity against human SUP-M2 cells harboring NPM-ALK after 72 hrs by MTT assay, IC50 = 0.174 μM. 24785465
Antiproliferative assay NIH/3T3 72 hrs Antiproliferative activity against crizotinib-resistant mouse NIH/3T3 cells harboring EML4-ALK variant 1/L1196M mutant after 72 hrs by MTT assay, IC50 = 0.606 μM. 24785465
Function assay NIH-3T3 1 hr Inhibition of wild type human EML4-fused ALK expressed in mouse NIH-3T3 cells assessed as phosphorylated ALK level after 1 hr by sandwich ELISA, IC50 = 0.08 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK F1174L mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.165 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK C1156Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.478 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK G1269A mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.605 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK S1206Y mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.626 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK L1196M mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 0.843 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK L1152R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 1.026 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK G1202R mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 1.148 μM. 24819116
Function assay NIH-3T3 1 hr Inhibition of human EML4-fused ALK 1151Tins mutant expressed in mouse NIH-3T3 cells assessed as phospho-ALK level after 1 hr by sandwich ELISA, IC50 = 3.039 μM. 24819116
Function assay MKN845 1 hr Inhibition of c-Met phosphorylation in human MKN845 cells after 1 hr by western blotting, IC50 = 0.02 μM. 24900750
Function assay MKN845 90 mins Inhibition of c-Met phosphorylation in human MKN845 cells after 90 mins by Sandwich-ELISA, IC50 = 0.02 μM. 24900750
Function assay karpas 299 90 mins Inhibition of NPM-fused ALK phosphorylation (unknown origin) expressed in human karpas 299 cells after 90 mins by Sandwich-ELISA, IC50 = 0.11 μM. 24900750
Cytotoxicity assay NCI-H1993 48 hrs Cytotoxicity against human NCI-H1993 cells after 48 hrs by MTT assay, IC50 = 0.061 μM. 24900830
Cytotoxicity assay NIH/3T3 48 hrs Cytotoxicity against mouse NIH/3T3 cells after 48 hrs by MTT assay, IC50 = 0.364 μM. 24900830
Cytotoxicity assay A549 48 hrs Cytotoxicity against human A549 cells after 48 hrs by MTT assay, IC50 = 4.084 μM. 24900830
Cytotoxicity assay NCI-H1975 48 hrs Cytotoxicity against human NCI-H1975 cells after 48 hrs by MTT assay, IC50 = 7.551 μM. 24900830
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against cMET-amplified human EBC1 cells after 72 hrs, IC50 = 0.0069 μM. 24900831
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against ALK-dependent human KARPAS299 cells after 72 hrs, IC50 = 0.2 μM. 24900831
Antitumor assay BAF3 50 mg/kg 2 weeks Antitumor activity against mouse BAF3 cells expressing EML4-ALK fusion protein allografted in nude mouse assessed as tumor growth inhibition at 50 mg/kg, po qd for 2 weeks relative to vehicle-treated control 24900831
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs, IC50 = 0.021 μM. 25537530
Antiproliferative assay SNU5 72 hrs Antiproliferative activity against human SNU5 cells after 72 hrs, IC50 = 0.0204 μM. 26005523
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs, IC50 = 0.0218 μM. 26005523
Antiproliferative assay MKN45 72 hrs Antiproliferative activity against human MKN45 cells after 72 hrs, IC50 = 0.0381 μM. 26005523
Antiproliferative assay BAF3/TPR-Met 72 hrs Antiproliferative activity against mouse BAF3/TPR-Met cells after 72 hrs, IC50 = 0.1274 μM. 26005523
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against ALK-dependent human NCI-H3122 cells after 72 hrs, IC50 = 0.2612 μM. 26476749
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against human NCI-H3122 cells after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.032 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.056 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of wild type EML4-ALK (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.056 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK S1206Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.065 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK F1174L mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.081 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK C1156Y mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.144 μM. 26568289
Antiproliferative assay SMS-KCNR 72 hrs Antiproliferative activity against human SMS-KCNR cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.179 μM. 26568289
Antiproliferative assay Kelly 72 hrs Antiproliferative activity against human Kelly cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.211 μM. 26568289
Antiproliferative assay LAN5 72 hrs Antiproliferative activity against human LAN5 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.232 μM. 26568289
Antiproliferative assay DFCI76 72 hrs Antiproliferative activity against human DFCI76 cells expressing EML4-ALK L1152R mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.233 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK G1202R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.328 μM. 26568289
Antiproliferative assay SK-N-SH 72 hrs Antiproliferative activity against human SK-N-SH cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.37 μM. 26568289
Antiproliferative assay CHLA20 72 hrs Antiproliferative activity against human CHLA20 cells expressing EML4-ALK R1275Q mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.439 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK G1269A mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.512 μM. 26568289
Antiproliferative assay SH-SY5Y 72 hrs Antiproliferative activity against human SH-SY5Y cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.523 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK L1196M mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.549 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK L1152R mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.645 μM. 26568289
Antiproliferative assay SK-N-BE(2) 72 hrs Antiproliferative activity against human SK-N-BE(2) cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 0.71 μM. 26568289
Function assay Ba/F3 72 hrs Inhibition of EML4-ALK 1151Tins mutant (unknown origin) expressed in mouse Ba/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.857 μM. 26568289
Cytotoxicity assay BA/F3 72 hrs Cytotoxicity against mouse BA/F3 cells assessed as cell viability after 72 hrs by MTS assay, IC50 = 0.927 μM. 26568289
Antiproliferative assay LAN1 72 hrs Antiproliferative activity against human LAN1 cells expressing EML4-ALK F1174L mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.346 μM. 26568289
Antiproliferative assay SK-N-FI 72 hrs Antiproliferative activity against human SK-N-FI cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.469 μM. 26568289
Antiproliferative assay SK-N-AS 72 hrs Antiproliferative activity against human SK-N-AS cells expressing wild type EML4-ALK after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.473 μM. 26568289
Antiproliferative assay DFCI114 72 hrs Antiproliferative activity against human DFCI114 cells expressing EML4-ALK G1269A mutant after 72 hrs by CellTiter-Glo Luminescent Cell Viability Assay, EC50 = 1.615 μM. 26568289
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by SRB assay, IC50 = 0.019 μM. 26698536
Cytotoxicity assay EBC1 72 hrs Cytotoxicity against human EBC1 cells assessed as inhibition of cell proliferation after 72 hrs by sulforhodamine B assay, IC50 = 0.044 μM. 27017548
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against human KARPAS299 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.103 μM. 27131066
Antiproliferative assay SUP-M2 72 hrs Antiproliferative activity against human SUP-M2 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.112 μM. 27131066
Antiproliferative assay SU-DHL1 72 hrs Antiproliferative activity against human SU-DHL1 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.136 μM. 27131066
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB/CCK-8 assay, IC50 = 0.21 μM. 27131066
Function assay NCI-H3122 72 hrs Inhibition of ALK expressed in human NCI-H3122 cells assessed as cell growth inhibition after 72 hrs by SRB/CCK-8 assay, IC50 = 0.261 μM. 27131066
Antiproliferative assay NIH/3T3 72 hrs Antiproliferative activity against mouse NIH/3T3 cells expressing wild type EML4-ALK after 72 hrs by SRB/CCK-8 assay, IC50 = 0.283 μM. 27131066
Antiproliferative assay NIH/3T3 72 hrs Antiproliferative activity against mouse NIH/3T3 cells expressing EML4-ALK L1196 mutant after 72 hrs by SRB/CCK-8 assay, IC50 = 1.16 μM. 27131066
Antiproliferative assay ALK-positive KARPAS299 72 hrs Antiproliferative activity against human ALK-positive KARPAS299 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay, IC50 = 0.365 μM. 27144831
Antiproliferative assay ALK-negative U937 72 hrs Antiproliferative activity against human ALK-negative U937 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay, IC50 = 2.286 μM. 27144831
Cytotoxicity assay HepG2 72 hrs Cytotoxicity against human HepG2 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 3.7 μM. 27396929
Cytotoxicity assay MIAPaCa2 72 hrs Cytotoxicity against human MIAPaCa2 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 7.16 μM. 27396929
Cytotoxicity assay HCC827 72 hrs Cytotoxicity against human HCC827 cells assessed as growth inhibition after 72 hrs by MTT assay, IC50 = 7.25 μM. 27396929
Cytotoxicity assay KARPAS299 72 hrs Cytotoxicity against human KARPAS299 cells harboring NPM-ALK assessed as reduction in cell proliferation after 72 hrs by MTT assay, IC50 = 0.068 μM. 27474925
Cytotoxicity assay HCC78 72 hrs Cytotoxicity against human HCC78 cells harboring SLC34A2-ROS1 assessed as reduction in cell proliferation after 72 hrs by MTT assay, IC50 = 0.34 μM. 27474925
Antiproliferative assay SU-DHL1 72 hrs Antiproliferative activity against ALK constitutively activated human SU-DHL1 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.0923 μM. 27769623
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against ALK constitutively activated human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.1009 μM. 27769623
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against ALK constitutively activated human KARPAS299 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.1049 μM. 27769623
Function assay NIH/3T3 Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.08 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.08 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.165 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK F1174L mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.165 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.478 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK C1156Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.478 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK G1269A mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.605 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK G1269A mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.605 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK S1206Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.626 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK S1206Y mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.626 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK L1196M mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.843 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK L1196M mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 0.843 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK L1152R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 1.026 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK L1152R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 1.026 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK G1202R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 1.148 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK G1202R mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 1.148 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK 1151Tins mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 3.039 μM. 28431340
Function assay NIH/3T3 Inhibition of wild type EML4/ALK 1151Tins mutant (unknown origin) expressed in NIH/3T3 cells, IC50 = 3.039 μM. 28431340
Cytotoxicity assay EBC1 72 hrs Cytotoxicity against human EBC1 cells assessed as decrease in cell viability after 72 hrs by Cell Titer-Glo assay, Activity = 0.013 μM. 28755635
Cytotoxicity assay MKN45 72 hrs Cytotoxicity against human MKN45 cells assessed as decrease in cell viability after 72 hrs by Cell Titer-Glo assay, Activity = 0.022 μM. 28755635
Cytotoxicity assay PC3 72 hrs Cytotoxicity against human PC3 cells assessed as decrease in cell viability after 72 hrs by Cell Titer-Glo assay, Activity = 2.244 μM. 28755635
Function assay BAF3 72 hrs Inhibition of EML4-fused ALK (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM. 28850922
Function assay BAF3 72 hrs Inhibition of NPM-fused ALK (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM. 28850922
Function assay BAF3 72 hrs Inhibition of TEL-fused ALK (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.0003 μM. 28850922
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against human NCI-H3122 cells harboring EML4-fused ALK varian1 after 72 hrs by CellTiter-Glo assay, GI50 = 0.037 μM. 28850922
Antiproliferative assay NCI-H2228 72 hrs Antiproliferative activity against human NCI-H2228 cells harboring EML4-fused ALK varian3 after 72 hrs by CellTiter-Glo assay, GI50 = 0.073 μM. 28850922
Function assay BAF3 72 hrs Inhibition of TEL-fused ALK C1156Y mutant (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.15 μM. 28850922
Function assay BAF3 72 hrs Inhibition of full length ALK F1174L mutant (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.32 μM. 28850922
Function assay BAF3 72 hrs Inhibition of TEL-fused ALK G1202R mutant (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.43 μM. 28850922
Antiproliferative assay CHL 72 hrs Antiproliferative activity against CHL cells after 72 hrs by CellTiter-Glo assay, GI50 = 0.45 μM. 28850922
Function assay BAF3 72 hrs Inhibition of TEL-fused ALK L1196M mutant (unknown origin) expressed in mouse BAF3 cells assessed as decrease in cell proliferation after 72 hrs by CellTiter-Glo assay, GI50 = 0.59 μM. 28850922
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells after 72 hrs by CellTiter-Glo assay, GI50 = 1.1 μM. 28850922
Antiproliferative assay CHO 72 hrs Antiproliferative activity against CHO cells after 72 hrs by CellTiter-Glo assay, GI50 = 3.2 μM. 28850922
Antiproliferative assay NCI-H2228 72 hrs Antiproliferative activity against human NCI-H2228 cells after 72 hrs by MTT assay, IC50 = 2.5 μM. 29091425
Antiproliferative assay H2228/CR 72 hrs Antiproliferative activity against human H2228/CR cells after 72 hrs by MTT assay, IC50 = 10 μM. 29091425
Function assay H2228 0.5 uM 3 hrs Inhibition of ALK in human H2228 cells assessed as decrease in AKT phosphorylation at 0.5 uM after 3 hrs by Western blot method 29091425
Function assay Ba/F3 0.1 to 1 uM 72 hrs Inhibition of human wild type EML4 fused ALK expressed in mouse Ba/F3 cells assessed as decrease in cell proliferation at 0.1 to 1 uM preincubated for 72 hrs followed by methyl-3H-thymidine incorporation measured after 8 hrs by filter scintillation counte 29091425
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by MTT assay, IC50 = 0.087 μM. 29174809
Antiproliferative assay HCC78 72 hrs Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by MTT assay, IC50 = 0.17 μM. 29174809
Antiproliferative assay NCI-H2228 72 hrs Antiproliferative activity against human NCI-H2228 cells harboring EML4-ALK after 72 hrs by MTT assay, IC50 = 0.24 μM. 29174809
Antiproliferative assay NCI-H3122 48 hrs Antiproliferative activity against human NCI-H3122 cells after 48 hrs by MTT assay, IC50 = 0.8 μM. 29174814
Antiproliferative assay HCC78 48 hrs Antiproliferative activity against human HCC78 cells after 48 hrs by MTT assay, IC50 = 2 μM. 29174814
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by Alamarblue assay, IC50 = 0.013 μM. 29202410
Antiproliferative assay MKN45 72 hrs Antiproliferative activity against human MKN45 cells after 72 hrs by Alamarblue assay, IC50 = 0.022 μM. 29202410
Antiproliferative assay MCF7 72 hrs Antiproliferative activity against human MCF7 cells after 72 hrs by Alamarblue assay relative to control, IC50 = 0.045 μM. 29202410
Antiproliferative assay A549 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by Alamarblue assay relative to control, IC50 = 0.1343 μM. 29202410
Antiproliferative assay HCT116 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by Alamarblue assay relative to control, IC50 = 0.2536 μM. 29202410
Antiproliferative assay SGC7901 72 hrs Antiproliferative activity against human SGC7901 cells after 72 hrs by Alamarblue assay relative to control, IC50 = 0.3213 μM. 29202410
Antiproliferative assay NCI-H460 72 hrs Antiproliferative activity against human NCI-H460 cells after 72 hrs by Alamarblue assay, IC50 = 2.244 μM. 29202410
Antiproliferative assay COLO205 72 hrs Antiproliferative activity against human COLO205 cells after 72 hrs by Alamarblue assay, IC50 = 2.449 μM. 29202410
Antiproliferative assay PC3 72 hrs Antiproliferative activity against human PC3 cells after 72 hrs by Alamarblue assay, IC50 = 9.787 μM. 29202410
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.0486 μM. 29288940
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.0575 μM. 29288940
Antiproliferative assay SU-DHL1 72 hrs Antiproliferative activity against human SU-DHL1 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.155 μM. 29288940
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by SRB or CCK8 assay, IC50 = 0.176 μM. 29288940
Antiproliferative assay NCI-H3122 72 hrs Antiproliferative activity against human NCI-H3122 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.303 μM. 29288940
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK L1196M mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.34 μM. 29288940
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells harboring EML4-ALK G1202R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.564 μM. 29288940
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against mouse BAF3 cells harboring CD74-ROS1 G2032R mutant after 72 hrs by SRB or CCK8 assay, IC50 = 0.594 μM. 29288940
Antiproliferative assay BAF3 72 hrs Antiproliferative activity against IL3-stimulated mouse BAF3 cells after 72 hrs by SRB or CCK8 assay, IC50 = 0.644 μM. 29288940
Antiproliferative assay HCC78 72 hrs Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by SRB or CCK8 assay, IC50 = 0.889 μM. 29288940
qHTS assay TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
qHTS assay Saos-2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
qHTS assay RD qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
qHTS assay SK-N-SH qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
qHTS assay BT-12 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
qHTS assay MG 63 (6-TG R) qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
qHTS assay NB1643 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
qHTS assay OHS-50 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
qHTS assay LAN-5 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells 29435139
qHTS assay NB-EBc1 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells 29435139
qHTS assay SK-N-SH qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
qHTS assay Rh41 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
qHTS assay A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
qHTS assay Rh30 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells 29435139
qHTS assay BT-37 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells 29435139
qHTS assay MG 63 (6-TG R) qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells 29435139
qHTS assay Rh30 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells 29435139
qHTS assay OHS-50 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells 29435139
qHTS assay SJ-GBM2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
qHTS assay SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
qHTS assay NB-EBc1 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
qHTS assay LAN-5 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
qHTS assay Rh18 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
qHTS assay NB1643 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells 29435139
qHTS assay SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells 29435139
qHTS assay TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells 29435139
qHTS assay Rh18 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells 29435139
qHTS assay Saos-2 qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells 29435139
Antiproliferative assay EBC1 72 hrs Antiproliferative activity against human EBC1 cells after 72 hrs by Cell Titer-Glo assay, IC50 = 0.039 μM. 29602036
Function assay Hs578T 100 nM 30 mins Inhibition of hepsin-mediated conversion of Pro-HGF into active form in human Hs578T cells assessed as decrease in MET phosphorylation at 100 nM preincubated for 30 mins followed by recombinant human pro-HGF addition measured after 30 mins by immunoblot m 29701962
Function assay HCC1937 100 nM 30 mins Inhibition of hepsin-mediated conversion of Pro-HGF into active form in human HCC1937 cells assessed as decrease in MET phosphorylation at 100 nM preincubated for 30 mins followed by recombinant human pro-HGF addition measured after 30 mins by immunoblot 29701962
Antiproliferative assay NCI-H2228 72 hrs Antiproliferative activity against human NCI-H2228 cells harboring EML4-ALK after 72 hrs by MTT assay, IC50 = 0.087 μM. 30223120
Antiproliferative assay HCC78 72 hrs Antiproliferative activity against human HCC78 cells harboring SLC34A2-ROS1 after 72 hrs by MTT assay, IC50 = 0.17 μM. 30223120
Antiproliferative assay KARPAS299 72 hrs Antiproliferative activity against human KARPAS299 cells harboring NPM-ALK after 72 hrs by MTT assay, IC50 = 0.24 μM. 30223120
NB1 Growth Inhibition Assay IC50=91.98 nM SANGER
NCI-SNU-5 Growth Inhibition Assay IC50=105.75 nM SANGER
SR Growth Inhibition Assay IC50=126.31 nM SANGER
SF539 Growth Inhibition Assay IC50=204.24 nM SANGER
SU-DHL-1 Growth Inhibition Assay IC50=336.82 nM SANGER
SCC-3 Growth Inhibition Assay IC50=356.76 nM SANGER
DEL Growth Inhibition Assay IC50=369.9 nM SANGER
CTV-1 Growth Inhibition Assay IC50=596.48 nM SANGER
EM-2 Growth Inhibition Assay IC50=601.34 nM SANGER
MHH-CALL-2 Growth Inhibition Assay IC50=682.57 nM SANGER
KM12 Growth Inhibition Assay IC50=706.9 nM SANGER
KINGS-1 Growth Inhibition Assay IC50=749.75 nM SANGER
MEG-01 Growth Inhibition Assay IC50=857.66 nM SANGER
BV-173 Growth Inhibition Assay IC50=1.05997 μM SANGER
LAMA-84 Growth Inhibition Assay IC50=1.38282 μM SANGER
KARPAS-299 Growth Inhibition Assay IC50=1.40861 μM SANGER
K-562 Growth Inhibition Assay IC50=1.72269 μM SANGER
SK-LMS-1 Growth Inhibition Assay IC50=1.76867 μM SANGER
MOLT-16 Growth Inhibition Assay IC50=1.95575 μM SANGER
CMK Growth Inhibition Assay IC50=1.96159 μM SANGER
ST486 Growth Inhibition Assay IC50=2.43073 μM SANGER
CI-1 Growth Inhibition Assay IC50=2.49659 μM SANGER
KP-N-RT-BM-1 Growth Inhibition Assay IC50=2.70122 μM SANGER
ALL-PO Growth Inhibition Assay IC50=3.18207 μM SANGER
KS-1 Growth Inhibition Assay IC50=3.21225 μM SANGER
Becker Growth Inhibition Assay IC50=4.2393 μM SANGER
GDM-1 Growth Inhibition Assay IC50=4.24617 μM SANGER
BC-1 Growth Inhibition Assay IC50=4.49277 μM SANGER
NB14 Growth Inhibition Assay IC50=4.83524 μM SANGER
NOS-1 Growth Inhibition Assay IC50=5.33874 μM SANGER
MZ1-PC Growth Inhibition Assay IC50=5.82151 μM SANGER
A498 Growth Inhibition Assay IC50=6.08473 μM SANGER
EW-16 Growth Inhibition Assay IC50=6.37773 μM SANGER
NALM-6 Growth Inhibition Assay IC50=6.68387 μM SANGER
EB-3 Growth Inhibition Assay IC50=7.07233 μM SANGER
697 Growth Inhibition Assay IC50=9.24329 μM SANGER
Ramos-2G6-4C10 Growth Inhibition Assay IC50=9.59842 μM SANGER
KNS-81-FD Growth Inhibition Assay IC50=9.69653 μM SANGER
HUTU-80 Growth Inhibition Assay IC50=9.74642 μM SANGER
LS-411N Growth Inhibition Assay IC50=10.0567 μM SANGER
RPMI-8402 Growth Inhibition Assay IC50=10.116 μM SANGER
KU812 Growth Inhibition Assay IC50=10.2991 μM SANGER
EW-1 Growth Inhibition Assay IC50=10.4425 μM SANGER
HC-1 Growth Inhibition Assay IC50=10.4844 μM SANGER
NB69 Growth Inhibition Assay IC50=10.5043 μM SANGER
MFH-ino Growth Inhibition Assay IC50=10.8303 μM SANGER
CCRF-CEM Growth Inhibition Assay IC50=11.597 μM SANGER
SK-N-DZ Growth Inhibition Assay IC50=12.0436 μM SANGER
NCI-H720 Growth Inhibition Assay IC50=12.1705 μM SANGER
HCC1187 Growth Inhibition Assay IC50=12.2041 μM SANGER
IST-SL2 Growth Inhibition Assay IC50=12.4872 μM SANGER
KE-37 Growth Inhibition Assay IC50=12.7966 μM SANGER
HCC1599 Growth Inhibition Assay IC50=12.9069 μM SANGER
A4-Fuk Growth Inhibition Assay IC50=12.9586 μM SANGER
NKM-1 Growth Inhibition Assay IC50=13.2925 μM SANGER
BE-13 Growth Inhibition Assay IC50=13.7989 μM SANGER
MV-4-11 Growth Inhibition Assay IC50=14.0324 μM SANGER
OPM-2 Growth Inhibition Assay IC50=14.4085 μM SANGER
KARPAS-422 Growth Inhibition Assay IC50=14.5126 μM SANGER
RPMI-8226 Growth Inhibition Assay IC50=14.8915 μM SANGER
KARPAS-45 Growth Inhibition Assay IC50=15.7716 μM SANGER
SK-PN-DW Growth Inhibition Assay IC50=15.8631 μM SANGER
LC-2 Growth Inhibition Assay IC50=16.1506 μM SANGER
NCI-H1648 Growth Inhibition Assay IC50=16.254 μM SANGER
RL95-2 Growth Inhibition Assay IC50=16.3978 μM SANGER
KNS-42 Growth Inhibition Assay IC50=16.7274 μM SANGER
RPMI-6666 Growth Inhibition Assay IC50=16.9211 μM SANGER
SIG-M5 Growth Inhibition Assay IC50=17.1903 μM SANGER
VA-ES-BJ Growth Inhibition Assay IC50=17.7451 μM SANGER
MONO-MAC-6 Growth Inhibition Assay IC50=17.9312 μM SANGER
LAN-6 Growth Inhibition Assay IC50=18.7557 μM SANGER
A388 Growth Inhibition Assay IC50=19.3059 μM SANGER
SK-NEP-1 Growth Inhibition Assay IC50=20.2132 μM SANGER
TE-10 Growth Inhibition Assay IC50=20.5221 μM SANGER
HL-60 Growth Inhibition Assay IC50=20.9099 μM SANGER
MC116 Growth Inhibition Assay IC50=21.7221 μM SANGER
SW962 Growth Inhibition Assay IC50=21.7915 μM SANGER
NOMO-1 Growth Inhibition Assay IC50=22.6564 μM SANGER
CTB-1 Growth Inhibition Assay IC50=22.8671 μM SANGER
MRK-nu-1 Growth Inhibition Assay IC50=22.9074 μM SANGER
GR-ST Growth Inhibition Assay IC50=23.76 μM SANGER
HH Growth Inhibition Assay IC50=24.003 μM SANGER
NCI-H1963 Growth Inhibition Assay IC50=24.0782 μM SANGER
QIMR-WIL Growth Inhibition Assay IC50=24.8772 μM SANGER
CGTH-W-1 Growth Inhibition Assay IC50=25.0723 μM SANGER
LP-1 Growth Inhibition Assay IC50=25.6551 μM SANGER
NCI-H748 Growth Inhibition Assay IC50=26.5137 μM SANGER
PF-382 Growth Inhibition Assay IC50=27.2223 μM SANGER
ATN-1 Growth Inhibition Assay IC50=27.3732 μM SANGER
L-540 Growth Inhibition Assay IC50=27.6459 μM SANGER
LXF-289 Growth Inhibition Assay IC50=27.7519 μM SANGER
LS-513 Growth Inhibition Assay IC50=28.1807 μM SANGER
NCI-H1581 Growth Inhibition Assay IC50=30.3976 μM SANGER
ES6 Growth Inhibition Assay IC50=30.6899 μM SANGER
SW982 Growth Inhibition Assay IC50=30.8566 μM SANGER
DOHH-2 Growth Inhibition Assay IC50=31.5893 μM SANGER
DB Growth Inhibition Assay IC50=33.9431 μM SANGER
MPP-89 Growth Inhibition Assay IC50=34.1756 μM SANGER
LB831-BLC Growth Inhibition Assay IC50=34.5184 μM SANGER
NB5 Growth Inhibition Assay IC50=34.8535 μM SANGER
GB-1 Growth Inhibition Assay IC50=35.0469 μM SANGER
TE-15 Growth Inhibition Assay IC50=35.2238 μM SANGER
LC4-1 Growth Inhibition Assay IC50=35.3847 μM SANGER
NCI-H747 Growth Inhibition Assay IC50=36.1369 μM SANGER
NTERA-S-cl-D1 Growth Inhibition Assay IC50=38.7347 μM SANGER
SK-MM-2 Growth Inhibition Assay IC50=40.1146 μM SANGER
TGW Growth Inhibition Assay IC50=41.0563 μM SANGER
ONS-76 Growth Inhibition Assay IC50=42.4883 μM SANGER
CPC-N Growth Inhibition Assay IC50=42.9971 μM SANGER
ES4 Growth Inhibition Assay IC50=44.4153 μM SANGER
Daudi Growth Inhibition Assay IC50=45.0827 μM SANGER
MOLT-4 Growth Inhibition Assay IC50=45.0853 μM SANGER
HT-144 Growth Inhibition Assay IC50=46.726 μM SANGER
SW872 Growth Inhibition Assay IC50=48.1933 μM SANGER
D-283MED Growth Inhibition Assay IC50=48.3542 μM SANGER
NCI-H2126 Growth Inhibition Assay IC50=48.8476 μM SANGER
NCI-SNU-16 Growth Inhibition Assay IC50=49.2143 μM SANGER
CESS Growth Inhibition Assay IC50=49.5088 μM SANGER
A101D Growth Inhibition Assay IC50=49.9736 μM SANGER
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht 450.34 Formule

C21H22Cl2FN5O

 Opslag (vanaf de datum van ontvangst)
CAS-nr. 877399-52-5 SDF downloaden Opslag van stamoplossingen

Synoniemen PF-02341066 Smiles CC(C1=C(C=CC(=C1Cl)F)Cl)OC2=C(N=CC(=C2)C3=CN(N=C3)C4CCNCC4)N

Oplosbaarheid

In vitro
Batch:

DMSO : 9 mg/mL (19.98 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molariteitscalculator

Massa Concentratie Volume Molecuulgewicht
Verdunningscalculator Molecuulgewichtcalculator

In vivo
Batch:

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

mg/kg g μL

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH2O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC50/Ki
ROS1
(Cell-free assay)
<0.025 nM(Ki)
c-Met
(A549, MDA-MB-231, GTL-16, HT29, 786-O, Colo-205, A498 cells)
11 nM
ALK
(Karpas299 cells)
24 nM
In vitro

PF-2341066 vertoont vergelijkbare potentie tegen c-Met-fosforylering in mIMCD3 muizen- of MDCK hondenepitheelcellen met IC50 van respectievelijk 5 nM en 20 nM. Deze verbinding vertoont verbeterde of vergelijkbare activiteit tegen NIH3T3-cellen die zijn gemanipuleerd om c-Met ATP-bindingsplaatsmutanten V1092I of H1094R of de P-loop-mutant M1250T tot expressie te brengen met IC50 van respectievelijk 19 nM, 2 nM en 15 nM, vergeleken met NIH3T3-cellen die de wildtype-receptor tot expressie brengen met IC50 van 13 nM. Daarentegen wordt een duidelijke verschuiving in potentie van deze verbinding waargenomen tegen cellen die zijn gemanipuleerd om c-Met-activeringslusmutanten Y1230C en Y1235D tot expressie te brengen met IC50 van respectievelijk 127 nM en 92 nM, vergeleken met de wildtype-receptor. Het voorkomt ook krachtig de fosforylering van c-Met in NCI-H69- en HOP92-cellen, met IC50 van respectievelijk 13 nM en 16 nM, die de endogene c-Met-varianten R988C en T1010I tot expressie brengen. Deze verbinding is >1.000-voudig selectief voor de VEGFR2- en PDGFRβ RTK's, >250-voudig selectief voor IRK en Lck, en ∼40- tot 60-voudig selectief voor Tie2, TrkA en TrkB, dit alles vergeleken met c-Met. Het is 20- tot 30-voudig selectief voor RON- en Axl RTK's. Daarentegen vertoont deze verbinding een bijna equivalente IC50 van 24 nM tegen de nucleofosmine (NPM)-anaplastische lymfoomkinase (ALK) oncogene fusievariant van de ALK RTK die tot expressie wordt gebracht door de KARPAS299 menselijke anaplastische grootcellige lymfoom (ALCL) cellijn. Het remt c-Met-afhankelijke neoplastische fenotypes van kankercellen en angiogene fenotypes van endotheelcellen. Deze chemische stof onderdrukt de groei van menselijke GTL-16 maagcarcinoomcellen met een IC50 van 9,7 nM. Het induceert apoptose in GTL-16-cellen met een IC50 van 8,4 nM. Het remt HGF-gestimuleerde migratie en invasie van menselijke NCI-H441 longcarcinoomcellen met IC50 van respectievelijk 11 nM en 6,1 nM. Het remt MDCK-celverstrooiing met een IC50 van 16 nM. Het voorkomt HGF-gestimuleerde c-Met-fosforylering, celoverleving en Matrigel-invasie met IC50 van respectievelijk 11 nM, 14 nM en 35 nM. Bovendien voorkomt het serum-gestimuleerde HMVEC-vertakkende tubulogenese (vorming van vasculaire buizen) in fibrinegels. Het remt ook krachtig NPM-ALK-fosforylering in Karpas299- of SU-DHL-1 ALCL-cellen met een IC50 van 24 nM. Deze verbinding voorkomt krachtig celproliferatie, wat gepaard gaat met G(1)-S-fase celcyclusarrest en inductie van apoptose in ALK-positieve ALCL-cellen met IC50 van 30 nM, maar niet in ALK-negatieve lymfoomcellen. Bovendien voorkomt het osteosarcoomgedrag geassocieerd met primaire tumorgroei (d.w.z. proliferatie en overleving) en metastase (bijv. invasie en clonogeniteit).

Kinase Assay
Cellulaire kinasefosforylering ELISA-assays
Cellen worden gezaaid in 96-well platen in media aangevuld met 10% foetaal runderserum (FBS) en na 24 uur overgebracht naar serumvrije media [met 0,04% bovine serumalbumine (BSA)]. In experimenten die ligand-afhankelijke RTK-fosforylering onderzoeken, worden overeenkomstige groeifactoren tot 20 minuten toegevoegd. Na incubatie van cellen met deze verbinding gedurende 1 uur en/of geschikte liganden gedurende de aangegeven tijden, worden de cellen eenmaal gewassen met HBSS aangevuld met 1 mM Na3VO4, en worden proteïnelysaten uit de cellen gegenereerd. Vervolgens wordt de fosforylering van geselecteerde proteïnekinasen beoordeeld door middel van een sandwich ELISA-methode met behulp van specifieke vangantistoffen die worden gebruikt om 96-well platen te coaten en een detectie-antistof die specifiek is voor gefosforyleerde tyrosineresiduen. Antistof-gecoate platen worden (a) 's nachts bij 4°C geïncubeerd in aanwezigheid van proteïnelysaten; (b) zeven keer gewassen in 1% Tween 20 in PBS; (c) 30 minuten geïncubeerd in een mierikswortelperoxidase-geconjugeerde anti-totaal-fosfotyrosine (PY-20) antistof (1:500); (d) opnieuw zeven keer gewassen; (e) geïncubeerd in 3,3′,5,5′-tetramethylbenzidine-peroxidase-substraat om een colorimetrische reactie te initiëren die wordt gestopt door toevoeging van 0,09 N H2SO4; en (f) gemeten op absorptie bij 450 nm met behulp van een spectrofotometer.
In vivo

In het GTL-16-model toont PF-2341066 het vermogen om een duidelijke regressie van grote gevestigde tumoren (>600 mm3) te veroorzaken in zowel de 50 mg/kg/dag als de 75 mg/kg/dag behandelingscohorten, met een afname van 60% in het gemiddelde tumorvolume gedurende het 43-daagse toedieningsschema. In een andere studie toont deze verbinding het vermogen om de GTL-16-tumorgroei gedurende >3 maanden volledig te remmen, waarbij slechts 1 van de 12 muizen een significante toename van de tumorgroei vertoonde gedurende het 3-maandse behandelingsschema van 50 mg/kg/dag. In het NCI-H441 NSCLC-model wordt een afname van 43% in het gemiddelde tumorvolume waargenomen bij 50 mg/kg/dag gedurende de 38-daagse PF-2341066-toedieningscyclus. In het Caki-1 RCC-model wordt een afname van 53% in het gemiddelde tumorvolume waargenomen, geassocieerd met een afname van het volume van elke tumor met ten minste 30% bij 50 mg/kg/dag gedurende de 33-daagse PF-2341066-toedieningscyclus. Deze verbinding toont ook een bijna volledige preventie van de groei van gevestigde tumoren bij 50 mg/kg/dag in de U87MG-glioblastoom- of PC-3-prostaatcarcinoom-xenograftmodellen, met respectievelijk 97% of 84% remming op de laatste studiedag. Daarentegen remt deze chemische stof, oraal toegediend bij 50 mg/kg/dag, de tumorgroei niet significant in het MDA-MB-231-borstcarcinoommodel of het DLD-1-coloncarcinoommodel. Een significante dosisafhankelijke reductie van CD31-positieve endotheelcellen wordt waargenomen bij 12,5 mg/kg/dag, 25 mg/kg/dag en 50 mg/kg/dag in GTL-16-tumoren, wat aangeeft dat remming van MVD een dosisafhankelijke correlatie vertoont met antitumorale werkzaamheid. Deze verbinding vertoont een significante dosisafhankelijke reductie van menselijke VEGFA- en IL-8-plasmaspiegels in zowel de GTL-16- als U87MG-modellen. Een duidelijke remming van gefosforyleerde c-Met-, Akt-, Erk-, PLCλ1- en STAT5-niveaus wordt waargenomen in GTL-16-tumoren na orale toediening van deze verbinding. Orale toediening van deze chemische stof aan severe gecombineerde immunodeficiënte-beige muizen met Karpas299 ALCL-tumorxenografts leidt tot dosisafhankelijke antitumorale werkzaamheid met volledige regressie van alle tumoren bij de dosis van 100 mg/kg/dag binnen 15 dagen na de initiële toediening van de verbinding. Bovendien wordt de remming van belangrijke NPM-ALK-signaleringsmediatoren, waaronder fosfolipase C-gamma, signaaltransducers en activatoren van transcriptie 3, extracellulaire signaal-gereguleerde kinasen en Akt door deze verbinding waargenomen bij concentraties of dosisniveaus die correleerden met remming van NPM-ALK-fosforylering en -functie. Deze verbinding voorkomt osteosarcoomgedrag geassocieerd met primaire tumorgroei (bijv. proliferatie en overleving) en metastase (bijv. invasie en clonogeniteit). Bij naakte muizen behandeld met deze chemische stof via orale sondevoeding, worden de groei en geassocieerde osteolyse en extracorticale botmatrixvorming van osteosarcoomxenografts voorkomen door deze verbinding. Behandeling van c-MET-geamplificeerde GTL-16-xenografts met 50 mg/kg van deze verbinding veroorzaakt tumorregressie die geassocieerd is met een langzame vermindering van 18F-FDG-opname en een afname van de expressie van de glucosetransporter 1, GLUT-1.
Referenties
  • [4] https://pubmed.ncbi.nlm.nih.gov/21764800/
  • [5] https://pubmed.ncbi.nlm.nih.gov/22091388/
  • [6] https://pubmed.ncbi.nlm.nih.gov/25733882/

Toepassingen

Methoden Biomarkers Afbeeldingen PMID
Western blot pALK / pAKT / pERK / pS6 pROS1 / ROS1 pSTAT3 / STAT3 PARP / cleaved caspase-3 / Bax / Bcl-2 p-c-Met / c-Met p-mTOR
S1068-WB1
24675041
Immunofluorescence LC3 / lysosome SRC / Met α-tubulin cytochrome c p-ALK
S1068-IF1
26384345

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer Werving Aandoeningen Sponsor/medewerkers Startdatum Fasen
NCT06062810 Not yet recruiting
Non-Small Cell Lung Cancer
Han Xu M.D. Ph.D. FAPCR Sponsor-Investigator IRB Chair|Medicine Invention Design Inc
 March 28 2024 Phase 2|Phase 3
NCT04148066 Completed
Carcinoma Non-Small-Cell Lung
The Netherlands Cancer Institute|Roche Pharma AG
 July 17 2019 Not Applicable
NCT03947385 Recruiting
Metastatic Uveal Melanoma|Cutaneous Melanoma|Colorectal Cancer|Other Solid Tumors
IDEAYA Biosciences
 June 28 2019 Phase 1|Phase 2
NCT03672643 Terminated
ALK or ROS1-positive NSCLC
Pfizer
 January 28 2019 Phase 4
NCT03439215 Unknown status
Carcinoma Non-Small-Cell Lung
Fondazione Ricerca Traslazionale|Clinical research technology Srl
 June 13 2017 Phase 2

Technische ondersteuning

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Veelgestelde vragen

Vraag 1:
Could you tell me whether this compound represents the pure R-form, or is it the racemic mixture, so a combination of the S- and the R-form?

Antwoord:
Our S1068 is the R enantiomer (except batches 05 and 06, which are the racemate), and S7505 is the S enantiomer.