H3B-6527

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

一种有效的、高选择性的共价 FGFR4 抑制剂，IC50 <1.2 nM。

A potent, highly selective covalent FGFR4 inhibitor with IC50 of <1.2 nM, 250-fold selectivity over FGFR1-3 (IC50=320, 1290 and 1060 nM, respectively); displays liitle to no inhibitory activity against TAOK2, JNK2 and CSF1R (IC50=690, >10,000, and >10,000 nM); inhibits Hep3B celll viability with GI50 of 25 nM in ATP-based cell viability assay, inhibits proliferation and leads to apoptosis in HCC cell lines by inhibiting FGFR4 signaling; exhibits antitumor activity in the Hep3B human HCC xenograft mouse model.Liver Cancer Phase 1 Clinical.

H3B-6527 inhibits TAOK2, JNK2, and CSF1R with IC50s of 690 nM, >10000 nM, and >10000 nM, respectively. H3B-6527 (10-10000 nM; 72 hours) results in a GI50 value of 25 nM. H3B-6527 (10-10000 nM; 72 hours) leads cell death in HCC cell lines. H3B-6527 (0.1-1000 nM; 1 hour) decreases the levels of pERK1/2 in a dose-dependent manner with maximal inhibition occurring at 100 nM. H3B-6527 (1-1000 nM; 24 hours) causes a robust increase in CYP7A1 transcripts. Cell Proliferation Assay Cell Line:Hepatocellular carcinoma (HCC) cell line Hep3B Concentration:10, 100, 1000, 10000 nM Incubation Time:72 hours Result:Resulted in a GI50 value of 25 nM.Apoptosis Analysis Cell Line:Hepatocellular carcinoma (HCC) cell line Hep3B.Concentration:10, 100, 1000, 10000 nM Incubation Time:72 hours Result:Leaded cell death in HCC cell lines.Western Blot Analysis Cell Line:Hepatocellular carcinoma (HCC) cell line Hep3B Concentration:0.1, 0.3, 1, 3, 10, 100, 1000 nM.Incubation Time:1 hour Result:Decreased the levels of pERK1/2 in a dose-dependent manner with maximal inhibition occurring at 100 nM.RT-PCR Cell Line:Hepatocellular carcinoma (HCC) cell line Hep3B.Concentration:1, 10, 100, 1000 nM.Incubation Time:24 hours Result:Caused a robust increase in CYP7A1 transcripts.

H3B-6527 (10-300 mg/kg; orally; twice-daily; for 15 days) significantly inhibits tumor growth at the 300 and 100 mg/kg and does not inhibit tumor growth at 30 and 10 mg/kg. Animal Model:BALB/c nu/nu female mice approximately 8-week-old, weighing 18-20 g bearing Hep3B orthotopic xenografts in liver Dosage:10, 30, 100, 300 mg/kg Administration:Orally; twice-daily; for 15 days Result:Inhibited tumor growth at the 300 and 100 mg/kg twice-daily dose.

H3B 6527 | H3B6527

Angiogenesis

FGFR

FGFR

Cancer

Liver Cancer

1702259-66-2

629.543

C29H34Cl2N8O4

>98% (HPLC)

In Vitro:?DMSO : 2.5 mg/mL (3.97 mM)

C=CC(NC1=CC(N2CCN(CC)CC2)=CC=C1NC3=NC=NC(N(C(NC4=C(Cl)C(OC)=CC(OC)=C4Cl)=O)C)=C3)=O

N-[2-[[6-[[[(2,6-Dichloro-3,5-dimethoxyphenyl)amino]carbonyl]methylamino]-4-pyrimidinyl]amino]-5-(4-ethyl-1-piperazinyl)phenyl]-2-propenamide

(-20℃)

With Ice Pack

≥ 2 years