BI-882370

SKU: orb1296244

Description

BI-882370 is a potent and selective RAF kinase inhibitor with low nanomolar IC50 values against oncogenic BRAF(V600E), wild-type BRAF, and CRAF. It also exhibits activity against SRC family kinases. This inhibitor is a valuable research tool for studying MAPK pathway signaling in cancers, supporting both in vitro and in vivo preclinical investigations.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1392429-79-6
• MW: 569.67
• Purity: 99.07% (May vary between batches)
• Formula: C₂₈H₃₃F₂N₇O₂S
• SMILES: CCCS(=O)(=O)Nc1ccc(F)c(c1F)-n1cc(-c2cncnc2)c2nc(ccc12)N(C)C1CCN(CC)CC1
• Target: Raf
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:1 mg/mL (1.76 mM);DMSO:5 mg/mL (8.78 mM)

Bioactivity

• Target IC50:
  B-Raf (V600E):0.4 nM|B-Raf:0.6 nM|C-Raf:0.8 nM
• In Vivo:
  BI-882370 (deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks) demonstrates efficacy in mouse models of BRAF-mutant melanomas and colorectal carcinomas, surpassing Vemurafenib, Dabrafenib, or Trametinib. BI-882370 (p.o; 25 mg/kg; twice daily; 40 days) develops resistance within 3 weeks, but no resistance is observed during a 5-week second-line therapy with trametinib. BI-882370 (deliver orally; 60 mg/kg; once daily; 2 weeks) exhibits no toxicity in clinical chemistry, hematology, pathology, and toxicogenomics in rats.
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• In Vitro:
  BI-882370 (0.9-6000 nM; 3 days) inhibits proliferation of BRAF-mutant human melanoma and colorectal cancer cells (EC50: 1-10 nM). BI 882370 (0.1-100 nM, 0.1-3000 nM; 2 hours) reduces p-MEK1/2, p-ERK1/2, and cyclin D1/D2 expression in BRAFV600E-mutant A375 cells and induces phosphorylation of MEK1/2 and enhances phosphorylation of ERK1/2 in WT BRO cells (3-300 nM). BI 882370 (0.1-100 nM, 0.1-3000 nM; 24 hours) suppresses cyclin D1/D2 expression and induces Kip1/p27 expression at concentrations of 1 nM or higher in BRAFV600E-mutant A375 cells, with no effect on expression of cyclins D1/D2 or Kip1/p27 in WT BRO cells.
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• Cell Research:
  Cell Line: BRAF-mutant and WT melanoma cell lines (A101D, A375, SK-MEL-28, G-361, and BRO); Colorectal cancer cell lines (COLO 205, HT-29, LS411N, and HCT-116). Concentration: 0.9-6000 nM. Incubation Time: 3 days
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• Animal Research:
  Animal Model: Human melanoma xenografts in nude mice with BRAF-mutant melanomas and colorectal carcinomas cells (A375, COLO 205; G-361, HT-29 cells). Dosage: 25 mg/kg; 50 mg/kg. Administration: Deliver orally; 25 mg/kg, 50 mg/kg; twice daily; 2 weeks
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

C-Raf, B-Raf (V600E), B-Raf, BI882370, BI-882370, BI 882370, inhibit, Inhibitor, Raf kinases, Raf

Compound Identifiers

PubChem CID

60152613