SB-590885

• CAT Number: I003477
• CAS Number: 405554-55-4
• Molecular Formula: C₂₇H₂₇N₅O₂
• Molecular Weight: 453.54
• Purity: ≥95%
• Target: Raf
• Solubility: DMSO ≥12mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20C powder
• IC50: 0.16 nM (Ki)
• IUPAC Name: N,N-dimethyl-2-[4-[(4E)-4-(1-nitroso-2,3-dihydroinden-5-ylidene)-5-(1H-pyridin-4-ylidene)-1H-imidazol-2-yl]phenoxy]ethanamine
• InChI: InChI=1S/C27H27N5O2/c1-32(2)15-16-34-22-7-3-19(4-8-22)27-29-25(18-11-13-28-14-12-18)26(30-27)21-5-9-23-20(17-21)6-10-24(23)31-33/h3-5,7-9,11-14,17,28H,6,10,15-16H2,1-2H3,(H,29,30)/b26-21+
• InChIKey: DPCXEUSDRQOOGZ-YYADALCUSA-N
• SMILES: CN(C)CCOC1=CC=C(C=C1)C2=NC(=C3C=CC4=C(CCC4=C3)N=O)C(=C5C=CNC=C5)N2

SB590885 (CAT: I003477) is a potent inhibitor of B-Raf, a protein kinase involved in the MAPK/ERK signaling pathway. It functions by blocking the activity of mutated B-Raf kinases, which are frequently found in various cancers. By inhibiting B-Raf, SB590885 can potentially disrupt the aberrant signaling pathways in cancer cells and hinder their growth and proliferation. The compound has been studied for its potential therapeutic use in the treatment of cancer, particularly in cases with B-Raf mutations.

Reference

1. Cancer Res. 2006 Dec 1;66(23):11100-5.

Demonstration of a genetic therapeutic index for tumors expressing oncogenic BRAF
by the kinase inhibitor SB-590885.

King AJ(1), Patrick DR, Batorsky RS, Ho ML, Do HT, Zhang SY, Kumar R, Rusnak DW,
Takle AK, Wilson DM, Hugger E, Wang L, Karreth F, Lougheed JC, Lee J, Chau D,
Stout TJ, May EW, Rominger CM, Schaber MD, Luo L, Lakdawala AS, Adams JL,
Contractor RG, Smalley KS, Herlyn M, Morrissey MM, Tuveson DA, Huang PS.

Author information:
(1)Department of Oncology, MMPD CEDD, GlaxoSmithKline, Collegeville, Pennsylvania
19426, USA.

Oncogenic BRAF alleles are both necessary and sufficient for cellular
transformation, suggesting that chemical inhibition of the activated mutant
protein kinase may reverse the tumor phenotype. Here, we report the
characterization of SB-590885, a novel triarylimidazole that selectively inhibits
Raf kinases with more potency towards B-Raf than c-Raf. Crystallographic analysis
revealed that SB-590885 stabilizes the oncogenic B-Raf kinase domain in an active
configuration, which is distinct from the previously reported mechanism of action
of the multi-kinase inhibitor, BAY43-9006. Malignant cells expressing oncogenic
B-Raf show selective inhibition of mitogen-activated protein kinase activation,
proliferation, transformation, and tumorigenicity when exposed to SB-590885,
whereas other cancer cell lines and normal cells display variable sensitivities
or resistance to similar treatment. These studies support the validation of
oncogenic B-Raf as a target for cancer therapy and provide the first evidence of
a correlation between the expression of oncogenic BRAF alleles and a positive
response to a selective B-Raf inhibitor.