Home MAPK Raf inhibitor Belvarafenib

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Belvarafenib Raf inhibitor

Cat.No.S8853

Belvarafenib is a selective and orally bioavailable pan-RAF kinase inhibitor with IC50 values of 41 nM, 7 nM and 2 nM for BRAF WT, BRAF(V600E) and CRAF kinases, respectively.
Belvarafenib Raf inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 478.93

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Quality Control

Chemical Information, Storage & Stability

Molecular Weight 478.93 Formula

C23H16ClFN6OS

 Storage (From the date of receipt) 3 years -20°C powder
CAS No. 1446113-23-0 -- Storage of Stock Solutions

Synonyms HM95573, GDC5573, RG6185 Smiles CC1=C(C2=C(C=C1)C(=NC=C2)NC3=C(C(=CC=C3)Cl)F)NC(=O)C4=CSC5=C4N=CN=C5N

Solubility

In vitro
Batch:

DMSO : 96 mg/mL (200.44 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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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

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

Note: 1. Please make sure the liquid is clear before adding the next solvent.
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Mechanism of Action

Targets/IC50/Ki
CRAF [1]
(Cell-free assay)
2 nM
BRAF V600E [1]
(Cell-free assay)
7 nM
BRAF WT [1]
(Cell-free assay)
41 nM
In vitro

Biochemically assayed for over 120 kinases, HM95573 shows the high selectivity toward BRAF mutant and CRAF kinases. The half maximal inhibition concentrations (IC50) of HM95573 against BRAFWT, BRAFV600E and CRAF kinases are 41nM, 7nM and 2nM, respectively. The strongly inhibited kinases subsequent to RAF kinases appear to be CSF1R (44nM), DDR1 (77nM) and DDR2 (182 nM). HM95573 potently inhibits the growth of mutant BRAF melanoma cell lines such as A375 (IC50: 57 nM) and SK-MEL-28 (69 nM) and of mutant NRAS melanoma cell lines such as SK-MEL-2 (53 nM) and SK-MEL-30 (24 nM). In addition, the phosphorylations of MEK and ERK downstream kinases associated with cell proliferation are effectively inhibited with treatment of HM95573 in mutant BRAF and mutant NRAS melanoma cells. HM95573 inhibits the downstream signaling in melanoma cells even in the presence of HGF which is known to mediate innate resistance to RAF inhibitors[1].
In vivo

HM95573 shows the excellent antitumor activity in mouse models xenografted with both of BRAF mutation cell lines (e.g. A375 and SK-MEL-28) and NRAS mutation cell lines (such as SK-MEL-2 and SK-MEL-30)[1].
References

Clinical Trial Information

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

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04835805 Active not recruiting
Melanoma
Genentech Inc.
 May 13 2021 Phase 1
NCT03284502 Active not recruiting
Locally Advanced Solid Tumor|Metastatic Solid Tumor
Hanmi Pharmaceutical Company Limited
 May 22 2017 Phase 1

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