Home Protein Tyrosine Kinase FGFR inhibitor H3B-6527

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H3B-6527 FGFR inhibitor

Cat.No.S8675

H3B-6527 is a highly selective covalent FGFR4 inhibitor with an IC50 value of <1.2 nM and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nM respectively).
H3B-6527 FGFR inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 629.54

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Quality Control

Batch: Purity: 98.91%
98.91

Solubility

In vitro
Batch:

DMSO : 50 mg/mL (79.42 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

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In vivo
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Chemical Information, Storage & Stability

Molecular Weight 629.54 Formula

C29H34Cl2N8O4

 Storage (From the date of receipt)
CAS No. 1702259-66-2 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CCN1CCN(CC1)C2=CC(=C(C=C2)NC3=CC(=NC=N3)N(C)C(=O)NC4=C(C(=CC(=C4Cl)OC)OC)Cl)NC(=O)C=C

Mechanism of Action

Targets/IC50/Ki
FGFR4
(Cell-free assay)
<1.2 nM
In vitro

H3B-6527 shows robust inhibition of the target kinase FGFR4 with an IC50 value of <1.2 nmol/L and at least 250-fold selectivity over FGFR1-3 (IC50 values of 320, 1,290 and 1,060 nmol/L respectively). TAOK2, JNK2, and CSF1R are also less sensitive to this compound treatment with IC50 values of 690, >10,000, and >10,000 nmol/L, respectively. This chemical 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 this compound leads to cell death in HCC cell lines. It has the selectivity and the selective dependence on FGFR4 across cancer types.
In vivo

In the Hep3B human HCC xenograft mouse model, H3B-6527 shows 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 this compound as measured by CYP7A1 mRNA and pERK1/2 protein levels is dose dependent, with higher doses leading to sustained responses. Oral treatment of this chemical, 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.
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03424577 Completed
Healthy Participants
Eisai Inc.|H3 Biomedicine Inc.
 December 27 2017 Phase 1
NCT02834780 Completed
Advanced Hepatocellular Carcinoma|Hepatocellular Carcinoma|Liver Cancer|Liver Neoplasms|Hepatic Cancer|Hepatic Carcinoma
H3 Biomedicine Inc.|Eisai Inc.
 December 28 2016 Phase 1

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