ChemicalBook > CAS DataBase List > H3B-6527

H3B-6527

Product Name: H3B-6527
CAS No.: 1702259-66-2
Chemical Name: H3B-6527
Synonyms: CS-2347;H3B-6527;H3 Biomedicine;H3B6527;H3B 6527;Eisai/H3 Biomedicine;H3B-6527, 10 mM in DMSO;H-3B-6527,H3B6527,H3B 6527;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]-
CBNumber: CB23146613
Molecular Formula: C29H34Cl2N8O4
Formula Weight: 629.54
MOL File: 1702259-66-2.mol

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H3B-6527 Property

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

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Hazard and Precautionary Statements (GHS)

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N-Bromosuccinimide Price

Cayman Chemical

Product number: 26072
Product name: H3B-6527
Purity: ≥98%
Packaging: 1mg
Price: $81
Updated: 2024/03/01

Cayman Chemical

Product number: 26072
Product name: H3B-6527
Purity: ≥98%
Packaging: 5mg
Price: $238
Updated: 2024/03/01

Cayman Chemical

Product number: 26072
Product name: H3B-6527
Purity: ≥98%
Packaging: 10mg
Price: $435
Updated: 2024/03/01

Cayman Chemical

Product number: 26072
Product name: H3B-6527
Purity: ≥98%
Packaging: 25mg
Price: $887
Updated: 2024/03/01

AK Scientific

Product number: 2308EF
Product name: H3B-6527
Packaging: 1mg
Price: $187
Updated: 2021/12/16

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H3B-6527 Chemical Properties,Usage,Production

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

Raw materials

Preparation Products

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H3B-6527 Suppliers

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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

H3 Biomedicine

H3B-6527, 10 mM in DMSO

1702259-66-2

C29H34Cl2N8O4