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Alisertib (MLN8237) Aurora A Kinase-remmer

Name: Alisertib (MLN8237)
Brand: Selleck Chemicals
SKU: S1133
Rating: 5 (366 reviews)

Cat.nr.S1133

Alisertib (MLN8237) is een selectieve Aurora A-remmer met een IC50 van 1,2 nM in een celvrije assay, en het heeft een >200-voudig hogere selectiviteit voor Aurora A dan voor Aurora B. Deze verbinding induceert celcyclusarrest, apoptosis en autophagy. Fase 3.

Alisertib (MLN8237) Aurora Kinase remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 518.92

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Kwaliteitscontrole

Batch: Zuiverheid: 99.56%

99.56

Producten die vaak samen worden gebruikt met Alisertib (MLN8237)

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Volasertib (BI6727)

It and Volasertib inhibit AURKA and PLK1 and synergistically block cell cycle progression in diffuse midline glioma cells.

Gerelateerde doelwitten	CDK HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Casein Kinase
Overig Aurora Kinase Inhibitoren	Hesperadin Tozasertib (VX-680) ZM 447439 MLN8054 Danusertib (PHA-739358) MK-5108 TCS7010 (Aurora A Inhibitor I) AMG-900 PHA-680632 CCT137690

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Formulering	Activiteitsbeschrijving	PMID
HCT116	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=0.04 μM	26136684
LS174T	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=0.05 μM	26136684
T84	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=0.09 μM	26136684
LS180	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=1 μM	26136684
SW948	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=1 μM	26136684
HCT15	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50<0.4 μM	26136684
DLD-1	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50<0.8 μM	26136684
MIP-101	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=1 μM	26136684
SNU1544	Growth Inhibition Assay	0.5 μM	72 h	DMSO	IC50=1 μM	26136684
OCI-Ly10	Cytotoxic Assay		72 h	DMSO	IC50=0.058 μM	25878331
SU-DHL2	Cytotoxic Assay		72 h	DMSO	IC50=0.01 μM	25878331
OCI-LY7	Cytotoxic Assay		72 h	DMSO	IC50=0.081 μM	25878331
SU-DHL6	Cytotoxic Assay		72 h	DMSO	IC50=0.482 μM	25878331
Jeko-1	Cytotoxic Assay		72 h	DMSO	IC50=0.029 μM	25878331
JVM-2	Cytotoxic Assay		72 h	DMSO	IC50=0.01 μM	25878331
Rec-1	Cytotoxic Assay		72 h	DMSO	IC50=0.087 μM	25878331
Z-138	Cytotoxic Assay		72 h	DMSO	IC50=0.013 μM	25878331
H9	Cytotoxic Assay		72 h	DMSO	IC50=0.6 μM	25878331
HH	Cytotoxic Assay		72 h	DMSO	IC50=0.7 μM	25878331
DND41	Cytotoxic Assay		72 h	DMSO	IC50=0.1 μM	25878331
CCL119	Cytotoxic Assay		72 h	DMSO	IC50=0.062 μM	25878331
J.Cam 1.6	Cytotoxic Assay		72 h	DMSO	IC50=0.105 μM	25878331
Sup-T1	Cytotoxic Assay		72 h	DMSO	IC50=2.142 μM	25878331
Tib 152	Cytotoxic Assay		72 h	DMSO	IC50=0.8 μM	25878331
MCF7	Function Assay	5 μM	24 h	DMSO	Induces G2/M arrest	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Induces G3/M arrest	25834401
MCF7	Function Assay	5 μM	24 h	DMSO	Decreases the expression level of CDK1/CDC2	25834401
MCF7	Function Assay	5 μM	24 h	DMSO	Decreases the expression level of CDK2	25834401
MCF7	Function Assay	5 μM	24 h	DMSO	Decreases the expression level of cyclin B1	25834401
MCF7	Function Assay	5 μM	24 h	DMSO	Increases the expression level of p21 Waf1/Cip1	25834401
MCF7	Function Assay	5 μM	24 h	DMSO	Increases the expression level of p27 Kip1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Decreases the expression level of CDK1/CDC2	25834401
MDA-MB-231	Function Assay	1 μM	24 h	DMSO	Increases the expression level of CDK2	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Decreases the expression level of cyclin B1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Increases the expression level of p21 Waf1/Cip1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Increases the expression level of p27 Kip1	25834401
MDA-MB-231	Function Assay	5 μM	24 h	DMSO	Increases the expression level of p53	25834401
MCF7	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptotic death	25834401
MDA-MB-231	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptotic death	25834401
MCF7	Function Assay	1 μM	72 h	DMSO	Induces autophagic death	25834401
MDA-MB-231	Function Assay	1 μM	72 h	DMSO	Induces autophagic death	25834401
U-2 OS	Growth Inhibition Assay	50 μM	24 h	DMSO	IC50=16.6 μM	25792811
MG-63	Growth Inhibition Assay	50 μM	24 h	DMSO	IC50=9.5 μM	25792811
U-2 OS	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptotic cell death	25792811
MG-63	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptotic cell death	25792811
U-2 OS	Function Assay	5 μM	24 h	DMSO	Promotes autophagic cell death	25792811
MG-63	Function Assay	5 μM	24 h	DMSO	Promotes autophagic cell death	25792811
PANC-1	Growth Inhibition Assay	50 μM	24 h	DMSO	IC50=7.1 μM	25632225
BxPC-3	Growth Inhibition Assay	50 μM	24 h	DMSO	IC50=6.8 μM	25632225
PANC-1	Function Assay	5 μM	24 h	DMSO	Induces cell cycle arrest in G2/M phase	25632225
BxPC-3	Function Assay	5 μM	24 h	DMSO	Induces cell cycle arrest in G2/M phase	25632225
PANC-1	Function Assay	5 μM	24 h	DMSO	Induces autophagic cell death	25632225
BxPC-3	Function Assay	5 μM	24 h	DMSO	Induces autophagic cell death	25632225
SKOV3	Growth Inhibition Assay	100 μM	24 h	DMSO	IC50=20.48 μM	25624750
OVCAR4	Growth Inhibition Assay	100 μM	24 h	DMSO	IC50=22.13 μM	25624750
SKOV3	Function Assay	5 μM	72 h	DMSO	Induces G2/M arrest	25624750
OVCAR4	Function Assay	5 μM	72 h	DMSO	Induces G2/M arrest	25624750
SKOV3	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptosis	25624750
OVCAR4	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptosis	25624750
AGS	Growth Inhibition Assay	25 μM	24 h	DMSO	IC50=19.09 μM	25609923
NCI-N78	Growth Inhibition Assay	25 μM	24 h	DMSO	IC50=26.33 μM	25609923
AGS	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptosis	25609923
NCI-N78	Apoptosis Assay	5 μM	24 h	DMSO	Induces apoptosis	25609923
AGS	Function Assay	5 μM	24 h	DMSO	Induces the autophagy	25609923
NCI-N78	Function Assay	5 μM	24 h	DMSO	Induces the autophagy	25609923
HSC-3	Growth Inhibition Assay	1 μM	48 h		IC50=0.54 μM	25366143
GB30	Growth Inhibition Assay	1 μM	7 d	DMSO	IC50=0.011 μM	25106428
GB9	Growth Inhibition Assay	1 μM	7 d	DMSO	IC50=0.024 μM	25106428
GB169	Growth Inhibition Assay	1 μM	7 d	DMSO	IC50=0.032 μM	25106428
T24	Function Assay	1 μM	48 h	DMSO	Induces cell cycle arrest	23403633
RT4	Function Assay	1 μM	48 h	DMSO	Induces cell cycle arrest	23403633
UM-UC-3	Function Assay	1 μM	48 h	DMSO	Induces cell cycle arrest	23403633
T24	Apoptosis Assay	3.16 μM	96 h	DMSO	IC50=0.0306 μM	23403633
RT4	Apoptosis Assay	3.16 μM	96 h	DMSO	IC50=0.1198 μM	23403633
UM-UC-3	Apoptosis Assay	3.16 μM	96 h	DMSO	IC50=0.0449 μM	23403633
OVCAR-5	Function Assay	50 nM			Inhibits cell migration	23334327
SKOV3ip2	Function Assay	50 nM			Inhibits cell migration	23334327
S462	Growth Inhibition Assay	100 μM	72 h	DMSO	Attenuates cell growth	23328114
2884	Growth Inhibition Assay	100 μM	72 h	DMSO	Attenuates cell growth	23328114
2885	Growth Inhibition Assay	100 μM	72 h	DMSO	Attenuates cell growth	23328114
CRL-2396	Growth Inhibition Assay	100 μM		water	IC50=0.092 μM	23153524
TIB-48	Growth Inhibition Assay	100 μM		water	IC50=0.088 μM	23153524
CRL-2396	Cytotoxic Assay	1 μM	48 h	water	Induces apoptosis	23153524
TIB-48	Cytotoxic Assay	1 μM	48 h	water	Induces apoptosis	23153524
AGS	Cytotoxic Assay	0.5 μM	24 h	DMSO	Decreases cell survival	22972611
FLO-1	Cytotoxic Assay	0.5 μM	24 h	DMSO	Decreases cell survival	22972611
OE33	Cytotoxic Assay	0.5 μM	24 h	DMSO	Decreases cell survival	22972611
SKLMS	Cytotoxic Assay	75 nM	96 h		Induces apoptosis	22821997
Leio285	Cytotoxic Assay	75 nM	96 h		Induces apoptosis	22821997
Mes-Sa	Cytotoxic Assay	75 nM	96 h		Induces apoptosis	22821997
DAOY	Cytotoxic Assay	10 μM	72 h	DMSO	IC50=0.04 μM	22669335
IMR32	Cytotoxic Assay	10 μM	72 h	DMSO	IC50=0.03 μM	22669335
Molt-4	Cytotoxic Assay	10 μM	72 h	DMSO	IC50=0.02 μM	22669335
MOLM-13	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
HL-60	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
MV4-11	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
SKM-1	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
SH2	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
NOMO-1	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
OCL-AML2	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
PL-21	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
KG-1	Growth Inhibition Assay	3 μM	72 h		Diminishes cell viability	22488249
A172	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.120 μM	22274399
U87	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.105 μM	22274399
U251	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.100 μM	22274399
T98	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.125 μM	22274399
LN18	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.210 μM	22274399
LN443	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.220 μM	22274399
HF66	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.225 μM	22274399
HF2303	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.060 μM	22274399
HF2359	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.060 μM	22274399
HF2414	Cytotoxic Assay	100 μM	24 h	DMSO	IC50=0.080 μM	22274399
A-673	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.032 μM	21448591
TC-32	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.039 μM	21448591
TC-71	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.102 μM	21448591
SK-N-MC	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.072 μM	21448591
CHLA-9	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.018 μM	21448591
CHLA-10	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.060 μM	21448591
CHLA-25	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.168 μM	21448591
CHLA-32	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.136 μM	21448591
CHLA-56	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=10 μM	21448591
CHLA-258	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.132 μM	21448591
COG-E-352	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.043 μM	21448591
CHLA-90	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.061 μM	21448591
CHLA-119	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.022 μM	21448591
CHLA-122	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.019 μM	21448591
CHLA-136	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.039 μM	21448591
CHLA-140	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.026 μM	21448591
LA-N-6	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.054 μM	21448591
NB-1643	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.037 μM	21448591
NB-EBc1	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.050 μM	21448591
SK-N-BE-1	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.028 μM	21448591
SK-N-BE-2	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.036 μM	21448591
SMS-KAN	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.034 μM	21448591
SMS-KANR	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.026 μM	21448591
SMS-KCN	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.019 μM	21448591
SMS-KCNR	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.010 μM	21448591
SMS-LHN	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.032 μM	21448591
SMS-MSN	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.022 μM	21448591
SMS-SAN	Growth Inhibition Assay	10 μM	96 h	DMSO	IC50=0.020 μM	21448591
Granta-4	Cytotoxic Assay	10 μM	7 d		IC50=0.040 μM	21291867
DB	Cytotoxic Assay	10 μM	7 d		IC50=0.042 μM	21291867
RL	Cytotoxic Assay	10 μM	7 d		IC50=0.015 μM	21291867
K562	Growth Inhibition Assay	10 μM	96 h		IC50=0.087 μM	21091633
LAMA-84	Growth Inhibition Assay	10 μM	96 h		IC50=0.057 μM	21091633
MM15	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=0.13 μM	20382844
OPM1	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=0.03 μM	20382844
RPM1	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=10.32 μM	20382844
INA6	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=0.002 μM	20382844
OPM2	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=4.37 μM	20382844
MM1R	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=1.68 μM	20382844
DOX40	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=5.48 μM	20382844
LR5	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=2.53 μM	20382844
U266	Growth Inhibition Assay	4 μM	72 h	DMSO	IC50=1.43 μM	20382844
RD	Growth Inhibition Assay	10 μM	96 h		IC50=0.228 μM	20108338
Rh41	Growth Inhibition Assay	10 μM	96 h		IC50=0.090 μM	20108338
Rh30	Growth Inhibition Assay	10 μM	96 h		IC50=0.230 μM	20108338
BT-12	Growth Inhibition Assay	10 μM	96 h		IC50=0.060 μM	20108338
CHLA-266	Growth Inhibition Assay	10 μM	96 h		IC50=0.072 μM	20108338
TC-71	Growth Inhibition Assay	10 μM	96 h		IC50=0.102 μM	20108338
SJ-GBM2	Growth Inhibition Assay	10 μM	96 h		IC50=0.050 μM	20108338
NALM-6	Growth Inhibition Assay	10 μM	96 h		IC50=0.062 μM	20108338
COG-LL-317	Growth Inhibition Assay	10 μM	96 h		IC50=0.047 μM	20108338
RS4-11	Growth Inhibition Assay	10 μM	96 h		IC50=0.018 μM	20108338
MOLT-4	Growth Inhibition Assay	10 μM	96 h		IC50=0.026 μM	20108338
CCRF-CEM	Growth Inhibition Assay	10 μM	96 h		IC50=0.094 μM	20108338
Kasumi-1	Growth Inhibition Assay	10 μM	96 h		IC50=0.103 μM	20108338
Karpas-299	Growth Inhibition Assay	10 μM	96 h		IC50=0.038 μM	20108338
Ramos-RA1	Growth Inhibition Assay	10 μM	96 h		IC50=0.127 μM	20108338
GSS	Antiproliferative assay		72 hrs		Antiproliferative activity against human GSS cells after 72 hrs by WST8 assay, IC50 = 0.039 μM.	25625617
LU99A	Antiproliferative assay		72 hrs		Antiproliferative activity against human LU99A cells after 72 hrs by WST8 assay, IC50 = 0.062 μM.	25625617
HL60	Antiproliferative assay		72 hrs		Antiproliferative activity against human HL60 cells after 72 hrs by WST8 assay, IC50 = 0.074 μM.	25625617
LC2/ad	Antiproliferative assay		72 hrs		Antiproliferative activity against human LC2/ad cells after 72 hrs by WST8 assay, IC50 = 0.077 μM.	25625617
MKN45	Antiproliferative assay		72 hrs		Antiproliferative activity against human MKN45 cells after 72 hrs by WST8 assay, IC50 = 0.093 μM.	25625617
HCT116	Antiproliferative assay		72 hrs		Antiproliferative activity against human HCT116 cells after 72 hrs by WST8 assay, IC50 = 0.095 μM.	25625617
Lu116	Antiproliferative assay		72 hrs		Antiproliferative activity against human Lu116 cells after 72 hrs by WST8 assay, IC50 = 0.097 μM.	25625617
NCI-H358	Antiproliferative assay		72 hrs		Antiproliferative activity against human NCI-H358 cells after 72 hrs by WST8 assay, IC50 = 0.1 μM.	25625617
MIAPaCa2	Antiproliferative assay		72 hrs		Antiproliferative activity against human MIAPaCa2 cells after 72 hrs by WST8 assay, IC50 = 0.13 μM.	25625617
PC14	Antiproliferative assay		72 hrs		Antiproliferative activity against human PC14 cells after 72 hrs by WST8 assay, IC50 = 0.17 μM.	25625617
HT-29	Antiproliferative assay		72 hrs		Antiproliferative activity against human HT-29 cells after 72 hrs by WST8 assay, IC50 = 0.33 μM.	25625617
HCT15	Antiproliferative assay		72 hrs		Antiproliferative activity against human HCT15 cells after 72 hrs by WST8 assay, IC50 = 0.74 μM.	25625617
Sf9	Function assay				Competitive inhibition of recombinant mouse aurora kinase A expressed in insect Sf9 cells in presence of ATP, Ki = 0.0003 μM.	26101564
Sf9	Function assay				Inhibition of recombinant mouse aurora kinase A expressed in insect Sf9 cells using biotin-GLRRASLG as substrate in presence of [gamma-33P]ATP, IC50 = 0.001 μM.	26101564
HCT116	Function assay				Inhibition of aurora kinase A autophosphorylation at T288 in human HCT116 cells by immunofluorescence analysis, IC50 = 0.007 μM.	26101564
HCT116	Cytotoxicity assay				Cytotoxicity against human HCT116 cells assessed as inhibition of cell proliferation by BrdU incorporation assay, GI50 = 0.03 μM.	26101564
HCT116	Function assay				Inhibition of aurora kinase B in human HCT116 cells assessed as inhibition of histone H3 phosphorylation by immunofluorescence analysis, IC50 = 1.5 μM.	26101564
BL21 (DE3) Rosetta	Function assay		30 mins		Inhibition of His-tagged human Aurora A kinase (122 to 40 residues) expressed in Escherichia coli BL21 (DE3) Rosetta cells using biotinylated STK2 substrate incubated for 30 mins by HTRF assay, IC50 = 0.00004 μM.	27391133
HeLa Kyoto	Function assay		20 hrs		Inhibition of Aurora B kinase in human HeLa Kyoto cells assessed as effect on distribution of phspho-histone H3 ser10 level incubated for 20 hrs, IC50 = 0.0015 μM.	27391133
HeLa Kyoto	Function assay		20 hrs		Inhibition of Aurora A kinase autophosphorylation at Thr288 in human HeLa Kyoto cells incubated for 20 hrs, IC50 = 0.0067 μM.	27391133
multiple myeloma	Function assay				Suppression of cell mitosis in human multiple myeloma cells, IC50 = 0.003 μM.	28918096
Calu6	Antitumor assay	20 mg/kg	21 days		Antitumor activity against human Calu6 cells xenografted in mouse assessed as tumor growth inhibition at 20 mg/kg, po bid administered for 21 days	26101564
HeLa Kyoto	Function assay	0.25 uM	20 hrs		Inhibition of Aurora A kinase localization at spindle microtubules in human HeLa Kyoto cells at 0.25 uM incubated for 20 hrs	27391133
MDA-MB-231	Function assay	1 uM	48 hrs		Induction of chromosome alignment defects in human MDA-MB-231 cells at 1 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	1 uM	48 hrs		Induction of aberrant spindle formation with tripolar and tetrapolar occurrence in human MDA-MB-231 cells at 1 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	0.5 uM	48 hrs		Inhibition of alpha-tubulin in human MDA-MB-231 cells assessed as abolishment of regular location of protein at 0.5 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
MDA-MB-231	Function assay	0.5 uM	48 hrs		Inhibition of AURKA in human MDA-MB-231 cells assessed as abolishment of regular location of protein at 0.5 uM after 48 hrs by DAPI staining based immunofluorescence assay	29358147
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
NB1643	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
MG 63 (6-TG R)	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
U-2 OS	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
SJ-GBM2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
NB-EBc1	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
LAN-5	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Rh18	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
SK-N-MC	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
TC32	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
Saos-2	qHTS assay				qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
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Chemische informatie, opslag en stabiliteit

Molecuulgewicht	518.92	Formule	C₂₇H₂₀ClFN₄O₄	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	1028486-01-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	COC1=C(C(=CC=C1)F)C2=NCC3=CN=C(N=C3C4=C2C=C(C=C4)Cl)NC5=CC(=C(C=C5)C(=O)O)OC

Oplosbaarheid

In vitro
Batch:

DMSO : 100 mg/mL (192.7 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:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 30%PEG300 2 5%Tween80 3 60%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	6.000mg/ml (11.56mM)	Taking the 1 mL working solution as an example, add 50 μL of 120 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 600 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo formulatiecalculator (heldere oplossing)

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

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

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

Kenmerken	First orally available inhibitor of Aurora A.
Targets/IC₅₀/Ki	Aurora A (Cell-free assay) 1.2 nM
In vitro	Alisertib (MLN8237) vertoont een >200-voudig hogere selectiviteit voor Aurora A dan de structureel verwante Aurora B met een IC50 van 396,5 nM, en heeft geen significante activiteit tegen 205 andere kinasen. Behandeling met deze verbinding (0,5 μM) remt de fosforylering van Aurora A in MM1.S- en OPM1-cellen, zonder de Aurora B-gemedieerde histon H3-fosforylering te beïnvloeden. Het remt significant de celproliferatie in multipel myeloom (MM) cellijnen met IC50-waarden van 0,003-1,71 μM, en vertoont een potentere antiproliferatieve activiteit tegen primaire MM-cellen en MM-cellijnen in aanwezigheid van BM-stromacellen, evenals IL-6 en IGF-1, dan tegen MM-cellen alleen. Bij 0,5 μM induceert het een 2- tot 6-voudige toename in de G2/M-fase in primaire MM-cellen en cellijnen, evenals significante apoptose en senescentie, waarbij de opregulatie van p53, p21 en p27, evenals PARP-, caspase 3- en caspase 9-splitsing betrokken is. Bovendien vertoont het een sterk synergetisch anti-MM-effect met Hexadecadrol, evenals een additief effect met doxorubicine en LDP-341. Behandeling met deze verbinding (0,5 μM) veroorzaakt de remming van de kolonieformatie van FLO-1, OE19 en OE33 slokdarmadenocarcinoomcellijnen, en induceert een significante toename van het percentage polyploïde cellen, en vervolgens een toename van het percentage cellen in de sub-G1-fase, wat verder kan worden versterkt in combinatie met NSC 119875 (2,5 μM), waarbij de hogere inductie van TAp73β, PUMA, NOXA, gesplitste caspase-3 en gesplitste PARP betrokken is in vergelijking met een behandeling met een enkel agens.
Kinase Assay	Aurora A radioactieve Flashplate enzymtest
Kinase Assay	Een Aurora A radioactieve Flashplate enzymtest wordt uitgevoerd om de aard en mate van remming te bepalen die wordt gemedieerd door Alisertib (MLN8237) in vitro. Recombinant Aurora A wordt tot expressie gebracht in Sf9-cellen en gezuiverd met GST-affiniteitschromatografie. Het peptidesubstraat voor Aurora A is geconjugeerd met biotine (Biotin-GLRRASLG). Aurora A-kinase (5 nM) wordt getest in 50 mM Hepes (pH 7,5), 10 mM MgCl₂, 5 mM DTT, 0,05% Tween 20, 2 μM peptidesubstraat, 3,3 μCi/mL [γ-³³P]ATP bij 2 μM, en toenemende concentraties van deze verbinding met behulp van Image FlashPlates.
In vivo	Alisertib (MLN8237) vermindert de tumorlast significant met een tumorgroeiremming (TGI) van respectievelijk 42% en 80% bij 15 mg/kg en 30 mg/kg, en verlengt de overleving van muizen vergeleken met de controle.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/22016509/ [2] https://pubmed.ncbi.nlm.nih.gov/20382844/ [3] https://pubmed.ncbi.nlm.nih.gov/22302096/

Toepassingen

Methoden	Biomarkers	PMID
Western blot	p-AURKA(T288) / p-EIF4E(S209) / c-Myc phospho-Aurora A / Aurora B H3S10P / H3K27me2 / H3K27me3 / H3K9me2 / H3AcK / H4K16Ac	28073841
Growth inhibition assay	Cell viability	25632225
Immunofluorescence	acetylated α-tubulin / γ-tubulin E-cadherin / β-catenin / vimentin / p-SMAD5 Centrin-2 / tubulin phospho-Aurora A(T288)	29401581

Informatie over klinische proeven

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

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT04479306	Completed	Recurrent Lung Non-Small Cell Carcinoma\|Stage IIIB Lung Cancer AJCC v8\|Stage IV Lung Cancer AJCC v8\|Stage IVA Lung Cancer AJCC v8\|Stage IVB Lung Cancer AJCC v8	M.D. Anderson Cancer Center	June 18 2020	Phase 1
NCT02812056	Withdrawn	Malignant Neoplasms of Digestive Organs\|Malignant Neoplasms of Female Genital Organs\|Malignant Neoplasms of Lip Oral Cavity and Pharynx\|Malignant Neoplasms of Male Genital Organs	M.D. Anderson Cancer Center\|Millennium Pharmaceuticals Inc.	September 2016	Phase 1
NCT02719691	Completed	Metastatic Breast Cancer\|Solid Tumors	University of Colorado Denver	May 13 2016	Phase 1
NCT02367352	Terminated	Advanced Solid Tumors\|Ovarian Cancer\|Small Cell Lung Cancer	Millennium Pharmaceuticals Inc.\|Takeda	March 19 2015	Phase 1

Technische ondersteuning

Gebruiksaanwijzing

Tel: +1-832-582-8158 Ext:3

Als u nog andere vragen heeft, laat dan een bericht achter.

Veelgestelde vragen

Vraag 1:
What is the suggested formulation of this compound for mouse injection(i.p.)?

Antwoord:
It can be dissolved in 6% DMSO/50% PEG 300/5% Tween 80/ddH2O at 10 mg/ml as a clear solution.

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