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Twochem Co.Ltd |
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| | H3B-6527 Basic information |
| Product Name: | H3B-6527 | | Synonyms: | H3B-6527;N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide;Eisai/H3 Biomedicine;H3B-6527, 98%, a highly selective FGFR4 inhibitor with potent antitumour activity;CS-2347;H3B6527;H3B 6527;2-Propenamide, N-[2-[[6-[[[(2,6-dichloro-3,5-dimethoxyphenyl)amino]carbonyl]methylamino]-4-pyrimidinyl]amino]-5-(4-ethyl-1-piperazinyl)phenyl]-;H-3B-6527,H3B6527,H3B 6527 | | CAS: | 1702259-66-2 | | MF: | C29H34Cl2N8O4 | | MW: | 629.54 | | EINECS: | | | Product Categories: | | | Mol File: | 1702259-66-2.mol |  |
| | H3B-6527 Chemical Properties |
| Boiling point | 832.1±65.0 °C(Predicted) | | density | 1.373±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | DMSO:50.0(Max Conc. mg/mL);79.42(Max Conc. mM) | | form | A solid | | pka | 11.00±0.70(Predicted) | | color | White to khaki |
| | H3B-6527 Usage And Synthesis |
| Uses | H3B-6527 is an orally active, highly selective and covalent FGFR4 inhibitor with an IC50 of <1.2 nM. H3B-6527 has at least 250-fold selectivity over FGFR1-3 with IC50s of 320 nM, 1290 nM and 1060 nM respectively. H3B-6527 has potent anti-cancer activity[1]. | | Biological Activity | H3B-6527 is a highly selective covalent FGFR4 inhibitor with IC50 < 1.2 nM, with >250-fold selectivity for FGFR4 over FGFR1-3 (IC50s of 320, 1290 and 1290 for FGFR1-3, respectively) 1060 nM). | | in vitro | H3B-6527 has a strong inhibitory effect on FGFR4 with IC50 less than 1.2 nM. TAOK2, JNK2 and CSF1R were less sensitive to H3B-6527 treatment with IC50s of 690, >10000 and >10000 nmol/L, respectively. Treatment of Hep3B cells with H3B-6527 resulted in a concentration-dependent activation of caspase-3/7. It inhibits FGFR4 signaling, inhibits proliferation, and causes apoptosis in HCC cells. | | in vivo | In a mouse model of Hep3B hepatocarcinoma xenografts, H3B-6527 had dose-proportional plasma exposure (greater than tumor exposure; doses tested were 30, 100, and 300 mg/kg). The pharmacodynamic response of H3B-6527 was detected, and it was found that CYP7A1 mRNA and pERK1/2 protein levels showed a concentration-dependent response, and higher concentrations would lead to a more durable response. In both subcutaneous Hep3B xenograft models and orthotopic xenograft models, oral administration of it (twice a day) significantly inhibited the growth of xenografts. Palbociclib enhanced the potency of it and promoted tumor regression in the JHH-7 model, whereas it single-agent administration only caused tumor growth arrest. | | IC 50 | FGFR4: <1.2 nM (IC50); FGFR1: 320 nM (IC50); FGFR2: 1290 nM (IC50); FGFR3: 1060 nM (IC50) | | References | [1] Joshi JJ, et al. H3B-6527 Is a Potent and Selective Inhibitor of FGFR4 in FGF19-Driven HepatocellularCarcinoma. Cancer Res. 2017 Dec 15;77(24):6999-7013. DOI:10.1158/0008-5472.CAN-17-1865 |
| | H3B-6527 Preparation Products And Raw materials |
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