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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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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

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

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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In vivo Formulation Calculator (Clear solution)

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Mechanism of Action

Targets/IC50/Ki
FGFR4 [1]
(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[1].
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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