Product Overview
BI-2865 is a potent, selective, non-covalent pan-KRAS inhibitor that targets both wild-type and mutant KRAS proteins. Unlike first-generation covalent KRAS G12C inhibitors such as sotorasib and adagrasib, BI-2865 binds to the inactive GDP-bound state of KRAS through non-covalent interactions, enabling inhibition of a broader range of KRAS mutations including G12C, G12D, G12V, and G13D, as well as wild-type KRAS.
Chemically, BI-2865 is (S)-2-amino-4-methyl-4-(3-(4-((S)-1-((S)-1-methylpyrrolidin-2-yl)ethoxy)pyrimidin-2-yl)-1,2,4-oxadiazol-5-yl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile with the molecular formula C₂₃H₂₇N₇O₂S and a molecular weight of 465.57 g/mol. It is a light yellow to brown solid with good solubility in DMSO.
Mechanism of Action
BI-2865 exerts its anticancer effects through unique mechanisms:
• Non-covalent Pan-KRAS Inhibition: Binds to the GDP-bound inactive state of KRAS with high affinity (Kd values of 6.9 nM for WT, 4.5 nM for G12C, 32 nM for G12D, 26 nM for G12V, and 4.3 nM for G13D)
• Nucleotide Exchange Inhibition: Blocks SOS-catalyzed nucleotide exchange, preventing KRAS activation
• Downstream Signaling Suppression: Inhibits the RAF-MEK-ERK signaling pathway, reducing cancer cell proliferation and survival
• Broad Mutant Coverage: Active against multiple KRAS mutations beyond G12C, addressing a major limitation of first-generation inhibitors
BI-2865 demonstrates potent anti-proliferative activity in BaF3 cells expressing various KRAS mutants with an average IC₅₀ of approximately 140 nM, making it a valuable tool for studying KRAS-driven cancers.
Research Applications & Significance
BI-2865 represents a significant advance in KRAS-targeted therapy research:
• Pan-KRAS Research: Enables study of KRAS biology across multiple mutation types, not just G12C
• Drug Resistance Studies: Useful for investigating resistance mechanisms to covalent KRAS G12C inhibitors
• Combination Therapy: Supports development of combination regimens with other targeted agents
• Preclinical Tool Compound: Serves as a reference compound for developing next-generation KRAS inhibitors
The KRAS mutation is one of the most common oncogenic drivers in human cancers, found in approximately 30% of all cancers including pancreatic, colorectal, and lung cancers. The development of pan-KRAS inhibitors like BI-2865 represents a major breakthrough in targeting this previously "undruggable" target.
Quality Specifications
Our BI-2865 is manufactured under strict quality control conditions:
• Purity: ≥98.0% determined by HPLC
• Identity confirmed by ¹H NMR and LC-MS
• Water content: ≤0.5%
• Enantiomeric excess: ≥99%
• Residual solvents: Meet ICH Q3C guidelines
• Each batch accompanied by comprehensive Certificate of Analysis (COA)
• Stable for 24 months when stored at -20°C in sealed containers protected from light
Packaging & Shipping
We offer flexible packaging options to meet diverse customer needs:
• Research quantities: 10mg, 50mg, 100mg amber glass vials
• Bulk quantities: 1g, 5g amber glass bottles
• Custom packaging available upon request
• Shipped with blue ice packs for temperature stability
• International shipping available with proper documentation
• Cold chain shipping available for large orders
