KRAS G12D inhibitor 14

• CAT Number: I044045
• CAS Number: 2765254-39-3
• Molecular Formula: C20H19F3N4OS
• Molecular Weight: 420.45
• Purity: ≥95%
• Synonyms: 4-(2,5-diazabicyclo[2.2.2]octan-2-yl)-6-[2-methoxy-5-(trifluoromethyl)phenyl]thieno[2,3-d]pyrimidine
• InChI: InChI=1S/C20H19F3N4OS/c1-28-16-5-2-11(20(21,22)23)6-14(16)17-7-15-18(25-10-26-19(15)29-17)27-9-12-3-4-13(27)8-24-12/h2,5-7,10,12-13,24H,3-4,8-9H2,1H3
• InChIKey: DYYANULKLUNJSO-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C=C1)C(F)(F)F)C2=CC3=C(N=CN=C3S2)N4CC5CCC4CN5

KRAS G12D inhibitor 14 is a potent KRAS G12D inhibitor with a KD of 33 nM for binding to KRAS G12D protein. KRAS G12D inhibitor 14 decreases the active form of KRAS G12D (KRAS G12D-GTP) but not KRAS G13D[1].
KRAS G12D inhibitor 14 (compound KD-8) shows antiproliferative activity with an IC50 of 2.1 μM against three KRAS G12D-mutated cells (Panc1, SW1990 and CT26). KRAS G12D inhibitor 14 decreases the active form of KRAS (KRAS-GTP) in KRAS G12D mutated cancer cell lines (CT26 and SW1990) but not in KRAS G13D mutated cancer cell lines (HCT116). KD-8 also causes efficient apoptosis of SW1990 and CT26 cancer cells. KRAS G12D inhibitor 14 down-regulates the phosphorylated Raf and Erk in CT26 and SW1990 cancer cell lines but not in HeLa cells (KRAS WT)[1].
KRAS G12D inhibitor 14 (compound KD-8) (40 mg/kg or 60 mg/kg; i.p.) exhibits significant antitumor efficacy in a CT26 tumor model with a tumor growth inhibition (TGI) of 42% or 53% without causing apparent toxicity[1].

Reference

[1]. Li L, et al. Discovery of Thieno[2,3-d]pyrimidine-based KRAS G12D inhibitors as potential anticancer agents via combinatorial virtual screening. Eur J Med Chem. 2022;233:114243.
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