| Identification | Back Directory | [Name]
H3B-6527 | [CAS]
1702259-66-2 | [Synonyms]
CS-2347
H3B-6527
H3B6527;H3B 6527
Eisai/H3 Biomedicine
H3B-6527, 98%, a highly selective FGFR4 inhibitor with potent antitumour activity
N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)-5-(4-ethylpiperazin-1-yl)phenyl)acrylamide
2-Propenamide, N-[2-[[6-[[[(2,6-dichloro-3,5-dimethoxyphenyl)amino]carbonyl]methylamino]-4-pyrimidinyl]amino]-5-(4-ethyl-1-piperazinyl)phenyl]- | [Molecular Formula]
C29H34Cl2N8O4 | [MDL Number]
MFCD30377210 | [MOL File]
1702259-66-2.mol | [Molecular Weight]
629.54 |
| Chemical Properties | Back Directory | [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 |
| Hazard Information | Back Directory | [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) | [storage]
Store at -20°C | [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 |
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