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H3B-6527
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
H3B-6527图片
CAS NO:1702259-66-2
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 629.54
Formula C29H34Cl2N8O4
CAS No. 1702259-66-2
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 50 mg/mL (79.4 mM)
Water: < 1mg/mL
Ethanol: < 1mg/mL
Solubility (In vivo)
Synonyms H3B-6527; H3B6527; H3B 6527
SMILES Code 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
实验参考方法
In Vitro

In vitro activity: H3B-6527 potently inhibits the FGFR4 kinase with an IC50 value of<1.2 290='' l='' and='' at='' least='' 250-fold='' selectivity='' over='' fgfr1-3='' ic50='' values='' of='' 060='' .='' csf1r='' are='' also='' less='' sensitive='' to='' h3b-6527='' treatment='' with=''>10,000, and>10,000 nmol/L, respectively. H3B-6527 inhibits FGFR4 signaling, proliferation, and leads to apoptosis in a HCC cell line (Hepatocellular carcinoma). Treatment on Hep3B cells leads to robust activation of caspase-3/7, an apoptotic marker, in a concentration-dependent manner, indicating FGFR4 inhibition by H3B-6527 leads to cell death in HCC cell lines. H3B-6527 has the selectivity and the selective dependence on FGFR4 across cancer types.


Kinase Assay:


Cell Assay: Hep3B cells were treated with H3B-6527 at 100 and 300 nmol/L for 0.5, 1, 2, 4, 8, and 24 hours and pERK1/2 levels are measured.

In VivoIn Hep3B human HCC xenograft mouse model, H3B-6527 displays dose-proportional plasma exposures and greater than dose-proportional tumor exposures within the dose range evaluated (30, 100, and 300 mg/kg). The pharmacodynamic response of H3B-6527 as measured by CYP7A1 mRNA and pERK1/2 protein levels is dose dependent, with higher doses leading to sustained responses. Oral treatment of H3B-6527, twice daily, inhibits xenograft growth in a dose-dependent manner in nude mice, with the 300 or 100 mg/kg twice daily, significantly inhibiting tumor growth in both Hep3B subcutaneous and orthotopic xenograft model and causing tumor regressions in the subcutaneous xenograft model. Palbociclib can enhance H3B-6527 efficacy and promote tumor regression in JHH-7 model where H3B-6527 as a single agent can only lead to tumor stasis.
Animal model BALB/c nu/nu female mice
Formulation & Dosage Formulated in 0.5% methylcellulose and 0.2% Tween80; 30, 100, and 300 mg/kg; P.O.
References Cancer Res. 2017 Dec 15;77(24):6999-7013.