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Belvarafenib Raf inhibitor

Name: Belvarafenib
Brand: Selleck Chemicals
SKU: S8853
Rating: 5 (4 reviews)

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.

Chemical Structure

Molecular Weight: 478.93

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Quality Control

Batch: Purity: 99.26%

99.26

Related Targets	ERK p38 MAPK JNK MEK Ras KRas S6 Kinase MAP4K TAK1 Mixed Lineage Kinase
Other Raf Inhibitors	LY3009120 Exarafenib (KIN-2787) GDC-0879 Avutometinib (Ro5126766, CH5126766) PLX-4720 AZ 628 SB590885 TAK-632 GW5074 RAF265 (CHIR-265)

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	1 year-80°Cin solvent 1 month-20°Cin solvent
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
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Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

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% DMSO + % + % Tween 80 + % ddH₂O

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Working concentration: mg/ml;

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.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	CRAF (Cell-free assay) 2 nM BRAF V600E (Cell-free assay) 7 nM BRAF WT (Cell-free assay) 41 nM
In vitro	Biochemically assayed for over 120 kinases, HM95573 shows 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 signalling in melanoma cells even in the presence of HGF which is known to mediate innate resistance to RAF inhibitors.
In vivo	HM95573 shows excellent antitumour activity in mouse models xenografted with both 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).
References	[1] http://www.hanmipharm.com/ehanmi/img/rnd/2015_AACR_(HM95573).pdf [2] https://pubmed.ncbi.nlm.nih.gov/34623791/ [3] https://aacrjournals.org/cancerres/article/75/15_Supplement/2606/601528/Abstract-2606-Antitumor-activity-of-the-selective

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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