GSK1324726A

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BET 溴结构域的有效选择性抑制剂，对于 BRD2/BRD3/BRD4 的 IC50 值分别为 41 nM/31 nM/22 nM。

A potent and selective inhibitor of BET bromodomain with IC50 of 41 nM/31 nM/22 nM for BRD2/BRD3/BRD4 respectively; exhibits growth inhibition with a median growth IC50 value of 75 nM in neuroblastoma cell lines; oral administration to mouse xenograft models of human neuroblastoma results in tumor growth inhibition and down-regulation MYCN and BCL2 expression.

A panel of neuroblastoma cell lines are treated with GSK1324726A (I-BET726), and observed potent growth inhibition and cytotoxicity in most cell lines irrespective of MYCN copy number or expression level. All neuroblastoma cell lines tested exhibit potent growth inhibition, with a median growth IC50 value (gIC50; inhibitor concentration resulting in 50% growth inhibition) equal to 75 nM.

GSK1324726A (I-BET726) inhibits neuroblastoma tumor growth. In the SK-N-AS model, mice in the vehicle group are euthanized on day 14 due to large tumor size. While there is no significant difference in tumor growth between the vehicle and GSK1324726A (5 mg/kg) group, 58% tumor growth inhibition (TGI) is observed in the GSK1324726A (15 mg/kg) group on day 14 of the study (n=9; p=0.006). Mice in the GSK1324726A (15 mg/kg) group are treated for an additional 7 days before tumor volume reaches a level comparable to that observed in the vehicle group, at which point the study is terminated. Tumors in the CHP-212 model grow much more slowly. After 42 days, tumors in vehicle-treated mice are only half the size those in the SK-N-AS model at the end of the study (Day 14). In the CHP-212 model, treatment with 5 mg/kg GSK1324726A results in TGI equal to 50% (n=8; p=0.1816), and mice in the 15 mg/kg group exhibits a TGI of 82% at the end of the study (n=5; p=0.0488).

I-BET726 | GSK 1324726A | GSK-1324726A | I-BET 726

Chromatin/Epigenetic

Bromodomain

BRD2|BRD3|BRD4

Cancer

——

1300031-52-0

434.9147

C25H23ClN2O3

>98% (HPLC)

DMSO: ≥ 46 mg/mL

O=C(O)C1=CC=C(C2=CC3=C(N(C(C)=O)[C@@H](C)C[C@H]3NC4=CC=C(Cl)C=C4)C=C2)C=C1

Benzoic acid, 4-[(2S,4R)-1-acetyl-4-[(4-chlorophenyl)amino]-1,2,3,4-tetrahydro-2-methyl-6-quinolinyl]-

(-20℃)

With Ice Pack

≥ 2 years