H3B-6527

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	同义名 :	-
	CAS号 :	1702259-66-2
	货号 :	A130690
	分子式 :	C₂₉H₃₄Cl₂N₈O₄
	纯度 :	99%+
	分子量 :	629.538
	MDL号 :	MFCD30377210
	存储条件：	Pure form Keep in dark place,Sealed in dry,2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	DMSO: 2 mg/mL(3.18 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
	动物实验配方：

生物活性
靶点	FGFR4 FGFR4, IC50:<1.2 nM
描述	Activation of the fibroblast growth factor receptor FGFR4 by fibroblast growth factor (FGF)19 drives hepatocellular carcinoma (HCC), a disease with few effective treatment options. H3B-6527 is a highly selective and orally available small molecule inhibitor of FGFR4 with an IC₅₀ less than 1.2 nM. In a HCC cell line Hep3B, H3B-6527 (1 nM; 24 h) caused a robust increase in CYP7A1 transcripts suggesting strong inhibition of the FGFR4 pathway by H3B-6527. Further, the levels of pERK1/2 decreased in a dose-dependent manner with maximal inhibition occurring at 100 nM of H3B-6527. In the Hep3B human HCC xenograft mouse model, treatment with H3B-6527 inhibited Hep3B xenograft growth, with the 300 and 100 mg/kg twice-daily doses significantly inhibiting growth and inducing CR (complete regression) or PR (partial regression) in 8 of 8 and 6 of 8 of mice, respectively (TGI (tumor growth inhibition) of 115 and 109%, P<0.05, for the 300 and 100 mg/kg treatment groups, respectively). H3B-6527 is currently undergoing evaluation in a phase I clinical trial in HCC^[3].
作用机制	H3B-6527 has an acrylamide group that forms a covalent bond via Michael addition with the Cys552 on FGFR4, present in the hinge region of the ATP-binding pocket^[2].

实验方案

1mg

5mg

10mg

1 mM

5 mM

10 mM

1.59mL

0.32mL

0.16mL

7.94mL

1.59mL

0.79mL

15.88mL

3.18mL

1.59mL

参考文献

[2]Rioux N, Kim A, Nix D, Bowser T, Warmuth M, Smith PG, Schindler J. Effect of a high-fat meal on the relative bioavailability of H3B-6527, a novel FGFR4 inhibitor, in healthy volunteers. Cancer Chemother Pharmacol. 2019 Jan;83(1):91-96

[3]Joshi JJ, Coffey H, Corcoran E. et al. H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven Hepatocellular Carcinoma. Cancer Res. 2017 Dec 15;77(24):6999-7013

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靶点

靶点	数值

FGFR4

FGFR4, IC50:<1.2 nM