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TAE684 (NVP-TAE684) ALK remmer

Name: TAE684 (NVP-TAE684)
Brand: Selleck Chemicals
SKU: S1108
Rating: 5 (83 reviews)

Cat.nr.S1108

TAE684 (NVP-TAE684) is een potente en selectieve ALK-remmer die de groei van ALCL-afgeleide en ALK-afhankelijke cellijnen blokkeerde met IC50-waarden tussen 2 en 10 nM, 100-voudig gevoeliger voor ALK dan InsR. Deze verbinding induceert celcyclusarrest en apoptose.

TAE684 (NVP-TAE684) ALK remmer Chemical Structure

Chemische structuur

Molecuulgewicht: 614.2

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Kwaliteitscontrole

Batch: Zuiverheid: 99.73%

99.73

Gerelateerde doelwitten	EGFR VEGFR PDGFR FGFR c-Met Src MEK CSF-1R FLT3 HER2
Overig ALK Inhibitoren	GSK1838705A Repotrectinib (TPX-0005) AZD3463 Ensartinib dihydrochloride AP26113-analog (ALK-IN-1) ASP3026 NVL-655 (Neladalkib) Envonalkib Belizatinib (TSR-011) HG-14-10-04

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Activiteitsbeschrijving
SCC-3	Growth Inhibition Assay	IC50=0.0000603 μM
SF539	Growth Inhibition Assay	IC50=0.000564 μM
DEL	Growth Inhibition Assay	IC50=0.000927 μM
NB1	Growth Inhibition Assay	IC50=0.00162 μM
SR	Growth Inhibition Assay	IC50=0.00277 μM
KARPAS-299	Growth Inhibition Assay	IC50=0.02384 μM
MHH-CALL-2	Growth Inhibition Assay	IC50=0.02952 μM
SU-DHL-1	Growth Inhibition Assay	IC50=0.04865 μM
A4-Fuk	Growth Inhibition Assay	IC50=0.05565 μM
EW-1	Growth Inhibition Assay	IC50=0.10256 μM
NOS-1	Growth Inhibition Assay	IC50=0.10294 μM
EW-16	Growth Inhibition Assay	IC50=0.10568 μM
TE-11	Growth Inhibition Assay	IC50=0.16096 μM
SW982	Growth Inhibition Assay	IC50=0.16478 μM
LAN-6	Growth Inhibition Assay	IC50=0.17443 μM
MZ1-PC	Growth Inhibition Assay	IC50=0.17835 μM
KS-1	Growth Inhibition Assay	IC50=0.19343 μM
PSN1	Growth Inhibition Assay	IC50=0.19631 μM
LC-2-ad	Growth Inhibition Assay	IC50=0.19692 μM
COLO-320-HSR	Growth Inhibition Assay	IC50=0.19776 μM
OPM-2	Growth Inhibition Assay	IC50=0.22669 μM
SK-NEP-1	Growth Inhibition Assay	IC50=0.23524 μM
ALL-PO	Growth Inhibition Assay	IC50=0.24524 μM
CMK	Growth Inhibition Assay	IC50=0.2553 μM
NCI-H1648	Growth Inhibition Assay	IC50=0.27855 μM
SIG-M5	Growth Inhibition Assay	IC50=0.29159 μM
TGBC24TKB	Growth Inhibition Assay	IC50=0.30218 μM
DOHH-2	Growth Inhibition Assay	IC50=0.31204 μM
NB69	Growth Inhibition Assay	IC50=0.31787 μM
MFH-ino	Growth Inhibition Assay	IC50=0.32523 μM
KP-N-RT-BM-1	Growth Inhibition Assay	IC50=0.33123 μM
MONO-MAC-6	Growth Inhibition Assay	IC50=0.33291 μM
ATN-1	Growth Inhibition Assay	IC50=0.33303 μM
NTERA-S-cl-D1	Growth Inhibition Assay	IC50=0.33396 μM
L-540	Growth Inhibition Assay	IC50=0.36988 μM
GB-1	Growth Inhibition Assay	IC50=0.38867 μM
MV-4-11	Growth Inhibition Assay	IC50=0.39446 μM
KG-1	Growth Inhibition Assay	IC50=0.39561 μM
OVCAR-4	Growth Inhibition Assay	IC50=0.40569 μM
NEC8	Growth Inhibition Assay	IC50=0.41292 μM
SK-MM-2	Growth Inhibition Assay	IC50=0.41609 μM
TE-8	Growth Inhibition Assay	IC50=0.4288 μM
697	Growth Inhibition Assay	IC50=0.43215 μM
NB14	Growth Inhibition Assay	IC50=0.43826 μM
GDM-1	Growth Inhibition Assay	IC50=0.47116 μM
HUTU-80	Growth Inhibition Assay	IC50=0.47375 μM
HL-60	Growth Inhibition Assay	IC50=0.48142 μM
OCI-AML2	Growth Inhibition Assay	IC50=0.48328 μM
ML-2	Growth Inhibition Assay	IC50=0.49031 μM
ES4	Growth Inhibition Assay	IC50=0.49109 μM
NCI-H747	Growth Inhibition Assay	IC50=0.4989 μM
RL95-2	Growth Inhibition Assay	IC50=0.50112 μM
TE-15	Growth Inhibition Assay	IC50=0.51124 μM
TE-12	Growth Inhibition Assay	IC50=0.53349 μM
LB1047-RCC	Growth Inhibition Assay	IC50=0.54549 μM
LB831-BLC	Growth Inhibition Assay	IC50=0.55023 μM
NCI-H1355	Growth Inhibition Assay	IC50=0.55184 μM
CTV-1	Growth Inhibition Assay	IC50=0.55624 μM
RXF393	Growth Inhibition Assay	IC50=0.55794 μM
SW872	Growth Inhibition Assay	IC50=0.56724 μM
MPP-89	Growth Inhibition Assay	IC50=0.57884 μM
RPMI-8226	Growth Inhibition Assay	IC50=0.63526 μM
LS-1034	Growth Inhibition Assay	IC50=0.6358 μM
SJSA-1	Growth Inhibition Assay	IC50=0.63725 μM
HOP-62	Growth Inhibition Assay	IC50=0.65033 μM
KGN	Growth Inhibition Assay	IC50=0.66168 μM
D-336MG	Growth Inhibition Assay	IC50=0.66169 μM
LS-411N	Growth Inhibition Assay	IC50=0.67462 μM
TE-1	Growth Inhibition Assay	IC50=0.69074 μM
LB996-RCC	Growth Inhibition Assay	IC50=0.69389 μM
TE-10	Growth Inhibition Assay	IC50=0.71496 μM
NCI-SNU-16	Growth Inhibition Assay	IC50=0.72664 μM
ES8	Growth Inhibition Assay	IC50=0.74975 μM
COLO-800	Growth Inhibition Assay	IC50=0.76695 μM
ES6	Growth Inhibition Assay	IC50=0.77559 μM
L-363	Growth Inhibition Assay	IC50=0.82375 μM
NMC-G1	Growth Inhibition Assay	IC50=0.83233 μM
LU-134-A	Growth Inhibition Assay	IC50=0.83912 μM
SF268	Growth Inhibition Assay	IC50=0.84042 μM
KARPAS-45	Growth Inhibition Assay	IC50=0.84263 μM
TGW	Growth Inhibition Assay	IC50=0.85863 μM
CHP-126	Growth Inhibition Assay	IC50=0.85957 μM
MOLT-16	Growth Inhibition Assay	IC50=0.87589 μM
LB771-HNC	Growth Inhibition Assay	IC50=0.89757 μM
NALM-6	Growth Inhibition Assay	IC50=0.90739 μM
GCIY	Growth Inhibition Assay	IC50=0.95526 μM
IST-MES1	Growth Inhibition Assay	IC50=0.98824 μM
LB2241-RCC	Growth Inhibition Assay	IC50=0.9884 μM
BL-70	Growth Inhibition Assay	IC50=0.99535 μM
NB17	Growth Inhibition Assay	IC50=1.00639 μM
LXF-289	Growth Inhibition Assay	IC50=1.03076 μM
TK10	Growth Inhibition Assay	IC50=1.05063 μM
K5	Growth Inhibition Assay	IC50=1.06274 μM
NCI-H716	Growth Inhibition Assay	IC50=1.07259 μM
HCE-T	Growth Inhibition Assay	IC50=1.08819 μM
GI-1	Growth Inhibition Assay	IC50=1.09798 μM
KARPAS-422	Growth Inhibition Assay	IC50=1.10022 μM
TE-9	Growth Inhibition Assay	IC50=1.11328 μM
SF126	Growth Inhibition Assay	IC50=1.11568 μM
BB30-HNC	Growth Inhibition Assay	IC50=1.13112 μM
NCI-H1304	Growth Inhibition Assay	IC50=1.13338 μM
HEL	Growth Inhibition Assay	IC50=1.14895 μM
HAL-01	Growth Inhibition Assay	IC50=1.15283 μM
SK-LMS-1	Growth Inhibition Assay	IC50=1.15974 μM
SW954	Growth Inhibition Assay	IC50=1.19567 μM
D-283MED	Growth Inhibition Assay	IC50=1.22379 μM
NCI-H1882	Growth Inhibition Assay	IC50=1.2389 μM
GI-ME-N	Growth Inhibition Assay	IC50=1.25208 μM
SK-PN-DW	Growth Inhibition Assay	IC50=1.26348 μM
C2BBe1	Growth Inhibition Assay	IC50=1.29117 μM
A704	Growth Inhibition Assay	IC50=1.32689 μM
KALS-1	Growth Inhibition Assay	IC50=1.3408 μM
ETK-1	Growth Inhibition Assay	IC50=1.34489 μM
LB647-SCLC	Growth Inhibition Assay	IC50=1.34986 μM
OCUB-M	Growth Inhibition Assay	IC50=1.36143 μM
NCI-H720	Growth Inhibition Assay	IC50=1.36378 μM
NB13	Growth Inhibition Assay	IC50=1.37293 μM
GR-ST	Growth Inhibition Assay	IC50=1.38757 μM
DU-4475	Growth Inhibition Assay	IC50=1.45853 μM
HCC2157	Growth Inhibition Assay	IC50=1.46659 μM
RKO	Growth Inhibition Assay	IC50=1.49922 μM
LS-123	Growth Inhibition Assay	IC50=1.51594 μM
NCI-H69	Growth Inhibition Assay	IC50=1.55811 μM
SW962	Growth Inhibition Assay	IC50=1.5613 μM
PF-382	Growth Inhibition Assay	IC50=1.5696 μM
A101D	Growth Inhibition Assay	IC50=1.57113 μM
NB10	Growth Inhibition Assay	IC50=1.57392 μM
NB5	Growth Inhibition Assay	IC50=1.58476 μM
HCE-4	Growth Inhibition Assay	IC50=1.6085 μM
HT-144	Growth Inhibition Assay	IC50=1.6319 μM
NCI-H524	Growth Inhibition Assay	IC50=1.64307 μM
NKM-1	Growth Inhibition Assay	IC50=1.6866 μM
KURAMOCHI	Growth Inhibition Assay	IC50=1.69573 μM
NCI-H187	Growth Inhibition Assay	IC50=1.70036 μM
U-266	Growth Inhibition Assay	IC50=1.73842 μM
BL-41	Growth Inhibition Assay	IC50=1.76272 μM
SK-N-DZ	Growth Inhibition Assay	IC50=1.78309 μM
Daudi	Growth Inhibition Assay	IC50=1.78967 μM
CPC-N	Growth Inhibition Assay	IC50=1.85096 μM
EM-2	Growth Inhibition Assay	IC50=1.851 μM
HCC1187	Growth Inhibition Assay	IC50=1.86241 μM
LP-1	Growth Inhibition Assay	IC50=1.87143 μM
CAS-1	Growth Inhibition Assay	IC50=1.98299 μM
NB7	Growth Inhibition Assay	IC50=2.00555 μM
VA-ES-BJ	Growth Inhibition Assay	IC50=2.01513 μM
SNU-C2B	Growth Inhibition Assay	IC50=2.03351 μM
LOXIMVI	Growth Inhibition Assay	IC50=2.06786 μM
NCI-H1581	Growth Inhibition Assay	IC50=2.11559 μM
IST-SL2	Growth Inhibition Assay	IC50=2.12445 μM
NOMO-1	Growth Inhibition Assay	IC50=2.17683 μM
TE-6	Growth Inhibition Assay	IC50=2.1905 μM
NCI-H526	Growth Inhibition Assay	IC50=2.19141 μM
MSTO-211H	Growth Inhibition Assay	IC50=2.20041 μM
LS-513	Growth Inhibition Assay	IC50=2.22269 μM
NCI-SNU-1	Growth Inhibition Assay	IC50=2.33256 μM
BB65-RCC	Growth Inhibition Assay	IC50=2.37493 μM
GT3TKB	Growth Inhibition Assay	IC50=2.39972 μM
OS-RC-2	Growth Inhibition Assay	IC50=2.42341 μM
NCI-H2126	Growth Inhibition Assay	IC50=2.43674 μM
SK-UT-1	Growth Inhibition Assay	IC50=2.47467 μM
DMS-114	Growth Inhibition Assay	IC50=2.61524 μM
ONS-76	Growth Inhibition Assay	IC50=2.63641 μM
8-MG-BA	Growth Inhibition Assay	IC50=2.65414 μM
BOKU	Growth Inhibition Assay	IC50=2.72764 μM
LAMA-84	Growth Inhibition Assay	IC50=2.79912 μM
ES1	Growth Inhibition Assay	IC50=2.81804 μM
NCI-H1395	Growth Inhibition Assay	IC50=2.82012 μM
A388	Growth Inhibition Assay	IC50=2.9617 μM
NCCIT	Growth Inhibition Assay	IC50=3.08862 μM
HD-MY-Z	Growth Inhibition Assay	IC50=3.13203 μM
NCI-H510A	Growth Inhibition Assay	IC50=3.18943 μM
NCI-N87	Growth Inhibition Assay	IC50=3.2002 μM
SCLC-21H	Growth Inhibition Assay	IC50=3.26859 μM
SH-4	Growth Inhibition Assay	IC50=3.28797 μM
QIMR-WIL	Growth Inhibition Assay	IC50=3.32849 μM
KM12	Growth Inhibition Assay	IC50=3.33544 μM
ST486	Growth Inhibition Assay	IC50=3.53883 μM
HC-1	Growth Inhibition Assay	IC50=3.62028 μM
BV-173	Growth Inhibition Assay	IC50=3.64088 μM
EW-24	Growth Inhibition Assay	IC50=3.66434 μM
LU-65	Growth Inhibition Assay	IC50=3.6871 μM
ECC4	Growth Inhibition Assay	IC50=3.7756 μM
ARH-77	Growth Inhibition Assay	IC50=4.11067 μM
BC-3	Growth Inhibition Assay	IC50=4.13068 μM
SNB75	Growth Inhibition Assay	IC50=4.2619 μM
MEG-01	Growth Inhibition Assay	IC50=4.27419 μM
NCI-H1417	Growth Inhibition Assay	IC50=4.28443 μM
MDA-MB-134-VI	Growth Inhibition Assay	IC50=4.30601 μM
Becker	Growth Inhibition Assay	IC50=4.47336 μM
DMS-153	Growth Inhibition Assay	IC50=4.66475 μM
TGBC1TKB	Growth Inhibition Assay	IC50=4.68515 μM
EW-3	Growth Inhibition Assay	IC50=4.76248 μM
KE-37	Growth Inhibition Assay	IC50=4.86196 μM
NCI-H23	Growth Inhibition Assay	IC50=4.87227 μM
MC116	Growth Inhibition Assay	IC50=4.94126 μM
NH-12	Growth Inhibition Assay	IC50=4.96439 μM
CTB-1	Growth Inhibition Assay	IC50=4.97721 μM
KM-H2	Growth Inhibition Assay	IC50=5.05323 μM
MOLT-4	Growth Inhibition Assay	IC50=5.1183 μM
NCI-H2141	Growth Inhibition Assay	IC50=5.14268 μM
EB-3	Growth Inhibition Assay	IC50=5.17504 μM
NCI-H1522	Growth Inhibition Assay	IC50=5.26322 μM
MRK-nu-1	Growth Inhibition Assay	IC50=5.43633 μM
no-11	Growth Inhibition Assay	IC50=5.47087 μM
CESS	Growth Inhibition Assay	IC50=5.58034 μM
KMOE-2	Growth Inhibition Assay	IC50=5.58659 μM
REH	Growth Inhibition Assay	IC50=6.25618 μM
KU812	Growth Inhibition Assay	IC50=6.42791 μM
SK-N-FI	Growth Inhibition Assay	IC50=6.60674 μM
MMAC-SF	Growth Inhibition Assay	IC50=7.06492 μM
RCC10RGB	Growth Inhibition Assay	IC50=7.22977 μM
NCI-H322M	Growth Inhibition Assay	IC50=7.33335 μM
NB6	Growth Inhibition Assay	IC50=7.54899 μM
MN-60	Growth Inhibition Assay	IC50=7.69215 μM
NCI-H1092	Growth Inhibition Assay	IC50=8.01734 μM
EKVX	Growth Inhibition Assay	IC50=8.47066 μM
D-263MG	Growth Inhibition Assay	IC50=8.55396 μM
NCI-H209	Growth Inhibition Assay	IC50=8.64006 μM
IST-SL1	Growth Inhibition Assay	IC50=8.89892 μM
ACN	Growth Inhibition Assay	IC50=9.19157 μM
MHH-PREB-1	Growth Inhibition Assay	IC50=9.21219 μM
EW-11	Growth Inhibition Assay	IC50=9.65396 μM
KASUMI-1	Growth Inhibition Assay	IC50=9.7877 μM
KINGS-1	Growth Inhibition Assay	IC50=10.2347 μM
EVSA-T	Growth Inhibition Assay	IC50=10.3192 μM
DSH1	Growth Inhibition Assay	IC50=10.3972 μM
COLO-824	Growth Inhibition Assay	IC50=10.8669 μM
K052	Growth Inhibition Assay	IC50=10.9322 μM
SK-MEL-2	Growth Inhibition Assay	IC50=10.9939 μM
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	614.2	Formule	C₃₀H₄₀ClN₇O₃S	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	761439-42-3	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	N/A			Smiles	CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=C(C=C(C=C3)N4CCC(CC4)N5CCN(CC5)C)OC

Oplosbaarheid

In vitro
Batch:

DMSO : 10 mg/mL (16.28 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.
Clear solution	10%DMSO 1 40%PEG300 2 5%TWEEN80 3 45%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.000mg/ml (1.63mM)	Taking the 1 mL working solution as an example, add 100 μL of 10 mg/ml clarified DMSO stock solution to 400 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 450 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.
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	30%PEG400 1 0.5%Tween80 2 5%propylene glycol, pH 4 Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	10.000mg/ml (16.28mM)	Taking the 1 mL working solution as an example, add 300 μL of 33.33 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol, pH 4, to the above system, mix evenly to clarify it; then continue Add 645 μL ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.

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

Targets/IC₅₀/Ki	ALK (Cell lines) 2-10 nM
In vitro	TAE684 (NVP-TAE684) vertoont geen significante kruisreactiviteit tegenover andere kinasen. Deze verbinding remt potent de proliferatie van Ba/F3 NPM-ALK-cellen met een IC50 van 3 nM, zonder de overleving van Ba/F3-cellen te beïnvloeden, zelfs bij 1 µM. Het remt ook de proliferatie van NPM-ALK-expresserende humane ALCL-cellijnen, waaronder Karpas-299 en SU-DHL-1, met een IC50 van 2–5 nM. Moleculaire modellering onthult dat L258 een van de belangrijkste kinase-selectiviteitsbepalende factoren voor dit chemische middel kan zijn. De behandeling resulteert in een snelle en aanhoudende remming van de fosforylering van NPM-ALK. De verbinding induceert apoptose en G1-fase-arrest in NPM-ALK-expresserende Ba/F3-cellen en ALCL-patiëntencellijnen. Het overwint aanzienlijk resistentie in H3122 CR-cellen, die het fusie-oncogen EML4-ALK bevatten, waardoor celgroei wordt verminderd, ALK-fosforylering wordt onderdrukt en apoptose wordt geïnduceerd. Neurietuitgroei geïnduceerd door expressie van het mALK R1279Q-mutant kon volledig worden geremd door deze verbinding bij 30 nM.
Kinase Assay	In vitro enzymtesten.
Kinase Assay	Alle in vitro enzymtesten worden uitgevoerd bij Upstate Biotechnology, met uitzondering van InsR en IGF-1R. Om de IC50 van TAE684 (NVP-TAE684) tegen InsR en IGF-1R te bepalen, wordt een homogene tijdopgeloste fluorescentietest uitgevoerd. ATP (10 mM) en 20 mg/ml gebiotinyleerd PolyEY (Glu, Tyr 4:1) worden gecombineerd met 50 nL seriële verdunningen van deze verbinding (10-500 nM) en 4 ng InsR-enzym in aanwezigheid van de kinasereactiebuffer (20 mM Tris-Cl, pH 7,5/10 mM MgCl₂/3 mM MnCl₂/1 mM DTT/10 mM NaVO₄/0,1 mg/ml BSA). De testen worden 1 uur bij omgevingstemperatuur geïncubeerd. Reacties worden beëindigd door 10 mL van de detectieoplossing toe te voegen, die 50 mM EDTA, 500 mM KF, 0,5 mg/ml BSA, 5 mg/mL Eu3+-cryptaat-gelabeld anti-fosfotyrosine-antilichaam Mab PT66-K en 5 mg/mL Streptavidin-XLent bevat. De reactie wordt een half uur geïncubeerd en fluorescentiesignalen worden afgelezen op Analyst GT.
In vivo	Na 4 weken behandeling met TAE684 (NVP-TAE684) bij 3 en 10 mg/kg is er een significante vertraging in de ontwikkeling van lymfoom en een 100- tot 1.000-voudige vermindering van het luminescentiesignaal, zonder tekenen van verbinding- of ziektegerelateerde toxiciteit in het Karpas-299 lymfoommodel. Deze verbindingstherapie induceert ook ziekteregressie in gevestigde Karpas-299-lymfomen en reguleert de CD30-expressie neerwaarts. Het vertoont ook indrukwekkende antitumoractiviteit tegen H3122 CR-xenografttumoren. Bovendien verbetert de behandeling met dit chemische middel het ruwe oogfenotype van beide ALK-mutanten, vooral dat waargenomen bij ALKR1275Q.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/17185414/ [2] https://pubmed.ncbi.nlm.nih.gov/21502504/ [3] https://pubmed.ncbi.nlm.nih.gov/21838707/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Growth inhibition assay	Cell viability		18594010
Western blot	p-ROS1 / ROS1 p-ALK / ALK / p-STAT3 / STAT3 / p-ERK / ERK / p-AKT / AKT / Survivin / BIM / PARP		25351743

Technische ondersteuning

Gebruiksaanwijzing

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

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

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