WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H561840
CAS#: 1446113-23-0 (free base)
Description: Belvarafenib, also known as GDC-5573, HM95573, RG6185, is a selective inhibitor of the RAF family kinases designed to inhibit the MAPK pathway, which is frequently activated in human tumors and drives tumor growth. ARAF mutants conferred resistance to belvarafenib in both a dimer- and a kinase activity-dependent manner. Belvarafenib induced ARAF mutant dimers, and dimers containing mutant ARAF were active in the presence of inhibitor. ARAF mutations may serve as a general resistance mechanism for RAF dimer inhibitors as the mutants exhibit reduced sensitivity to a panel of type II RAF inhibitors.
Hodoodo Cat#: H561840
Name: Belvarafenib
CAS#: 1446113-23-0 (free base)
Chemical Formula: C23H16ClFN6OS
Exact Mass: 478.08
Molecular Weight: 478.930
Elemental Analysis: C, 57.68; H, 3.37; Cl, 7.40; F, 3.97; N, 17.55; O, 3.34; S, 6.69
Related CAS #: 2344721-99-7 (HCl) 2344722-04-7 (2HCl) 1446113-23-0 (free base) 2344722-01-4 (tosylate) 2344722-06-9 (2 tosylate) 2344722-03-6 (mesylate) 2344722-08-1 (2 mesylate),
Synonym: Belvarafenib; GDC-5573; GDC5573; GDC 5573; HM95573; HM 95573; HM-95573; RG6185; RG-6185; RG 6185;
IUPAC/Chemical Name: 4-amino-N-(1-((3-chloro-2-fluorophenyl)amino)-6-methylisoquinolin-5-yl)thieno[3,2-d]pyrimidine-7-carboxamide
InChi Key: KVCQTKNUUQOELD-UHFFFAOYSA-N
InChi Code: InChI=1S/C23H16ClFN6OS/c1-11-5-6-13-12(7-8-27-22(13)30-16-4-2-3-15(24)17(16)25)18(11)31-23(32)14-9-33-20-19(14)28-10-29-21(20)26/h2-10H,1H3,(H,27,30)(H,31,32)(H2,26,28,29)
SMILES Code: O=C(C1=CSC2=C(N)N=CN=C21)NC3=C(C)C=CC4=C3C=CN=C4NC5=CC=CC(Cl)=C5F
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | Belvarafenib (HM95573) is a potent and pan RAF (Rapidly Accelerated Fibrosarcoma) inhibitor, with IC50s of 56 nM, 7 nM and 5 nM for B-RAF, B-RAFv600E and C-RAF respectively. |
| In vitro activity: | TBD |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 46.2 | 96.40 | |
| DMSO:PBS (pH 7.2) (1:2) | 0.3 | 0.69 | |
| DMF | 30.0 | 62.64 |
The following data is based on the product molecular weight 478.93 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | TBD |
| In vitro protocol: | TBD |
| In vivo protocol: | TBD |
1: Yen I, Shanahan F, Lee J, Hong YS, Shin SJ, Moore AR, Sudhamsu J, Chang MT, Bae I, Dela Cruz D, Hunsaker T, Klijn C, Liau NPD, Lin E, Martin SE, Modrusan Z, Piskol R, Segal E, Venkatanarayan A, Ye X, Yin J, Zhang L, Kim JS, Lim HS, Kim KP, Kim YJ, Han HS, Lee SJ, Kim ST, Jung M, Hong YH, Noh YS, Choi M, Han O, Nowicka M, Srinivasan S, Yan Y, Kim TW, Malek S. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma. Nature. 2021 Jun;594(7863):418-423. doi: 10.1038/s41586-021-03515-1. Epub 2021 May 5. PMID: 33953400.
2: Kim YY, Park H, Song T, Choi K, Dolton M, Mao J, Kim J, Ahn YG, Suh KH, Kim YH. Belvarafenib penetrates the BBB and shows potent antitumor activity in a murine melanoma brain metastasis model. Clin Exp Metastasis. 2023 Apr;40(2):137-148. doi: 10.1007/s10585-023-10198-7. Epub 2023 Feb 10. PMID: 36763292.
3: ARAF Mutations Limit Response to RAF Dimer Inhibition. Cancer Discov. 2021 Jul;11(7):1610. doi: 10.1158/2159-8290.CD-RW2021-069. Epub 2021 May 14. PMID: 33990346.
4: Awada G, Neyns B. Melanoma with genetic alterations beyond the BRAFV600 mutation: management and new insights. Curr Opin Oncol. 2022 Mar 1;34(2):115-122. doi: 10.1097/CCO.0000000000000817. PMID: 35050937.
5: Romany A, Liu R, Zhan S, Clayton J, Shen J. Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases. J Chem Inf Model. 2023 Apr 24;63(8):2483-2494. doi: 10.1021/acs.jcim.3c00014. Epub 2023 Apr 6. PMID: 37022803; PMCID: PMC10214248.
6: Tkacik E, Li K, Gonzalez-Del Pino G, Ha BH, Vinals J, Park E, Beyett TS, Eck MJ. Structure and RAF family kinase isoform selectivity of type II RAF inhibitors tovorafenib and naporafenib. J Biol Chem. 2023 May;299(5):104634. doi: 10.1016/j.jbc.2023.104634. Epub 2023 Mar 22. PMID: 36963492; PMCID: PMC10149214.
7: Roskoski R Jr. Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS. Pharmacol Res. 2021 Oct;172:105806. doi: 10.1016/j.phrs.2021.105806. Epub 2021 Aug 24. PMID: 34450320.
8: Rohrer L, Spohr C, Beha C, Griffin R, Braun S, Halbach S, Brummer T. Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase. Cell Commun Signal. 2023 Jun 14;21(1):136. doi: 10.1186/s12964-023-01146-9. PMID: 37316874; PMCID: PMC10265822.
