BI-2865

KRAS is an important protein in the RAS/MAPK signaling pathway that transmits signals from activated cell surface receptors leading to cell proliferation and survival. KRAS function is controlled by cycling through an inactive, GDP-bound state and an active, GTP-bound state. Activation of KRAS occurs when it binds to Guanine Nucleotide Exchange Factor (GEF) proteins, including SOS, which initiate the exchange of GDP for GTP. Active, GTP-bound KRAS can trigger activation of downstream signaling molecules including RAF, PI3K, and RAL. KRAS can self-inactivate by cleaving the terminal phosphate group on the GTP, converting it to GDP. This inactivation process is accelerated by GTPase-activating (GAP) proteins.KRAS has emerged as a target of significant clinical interest, due to mutations in the KRAS protein that promote the pathogenesis of 20-30% of human cancers. Testing a patient for the presence of specific KRAS mutants serves as a highly predictive marker for success rates to various types of lung and colon cancer therapies. The development of inhibitors against KRAS G12C, G12D, and G12V holds a promising future for oncology.

BI-2865 is a none-covalent pan-KRAS Inhibitor. BI-2865 binds to WT, G12C, G12D, G12V and G13D mutant KRAS with KDs of 6.9,4.5,32,26,4.3 nM respectively. BI-2865 inhibits the proliferation of G12C, G12D or G12V mutant KRAS expressing BaF3 cells (mean IC50: roughly 140 nM) .1

2937327-93-8

≥ 90%

Solid.

Soluble in DMSO up to 250 mg/mL.

C23H27N7O2S

Room Temperature

Powder-20°C3 years4°C2 yearsIn solvent-80°C6 months-20°C1 month