| Identification | Back Directory | [Name]
Benzo[b]thiophene-3-carbonitrile, 2-amino-4-[4-[(2S,5R)-2,5-dimethyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]-8-fluoro-2-[[(2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy]-6-(trifluoromethyl)-7-quinazolinyl]-7-fluoro-, (4S)- | [CAS]
2893809-51-1 | [Synonyms]
Benzo[b]thiophene-3-carbonitrile, 2-amino-4-[4-[(2S,5R)-2,5-dimethyl-4-(1-oxo-2-propen-1-yl)-1-piperazinyl]-8-fluoro-2-[[(2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl]methoxy]-6-(trifluoromethyl)-7-quinazolinyl]-7-fluoro-, (4S)- | [Molecular Formula]
C35H33F6N7O2S | [MOL File]
2893809-51-1.mol | [Molecular Weight]
729.74 |
| Chemical Properties | Back Directory | [Boiling point ]
855.8±75.0 °C(predicted) | [density ]
1.50±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
8.93±0.70(predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
BBO-8520 is a direct small molecule covalent inhibitor targeting KRAS G12C with high oral availability. BBO-8520 has the characteristics of KRAS G12C (OFF) inhibitor and the function of blocking KRAS G12C (ON) signal. BBO-8520 inhibits cell proliferation by inhibiting KRAS G12C (ON) by binding GTP protein. BBO-8520 can block RAS-RAF1 interaction and return KRAS G12C to the inactive (OFF) state [1]. | [in vivo]
BBO-8520 (10 mg/kg/d; po) causes inhibition of pERK and KRASG12C activation in a KrasG12C-p53-driven GEMM model, leading to durable tumor regression. BBO-8520 demonstrates strong dose-dependent and time-dependent pharmacodynamic effects (more than 80% inhibition of pERK) in mice with KRASG12C mutant tumors[1]. | [References]
[1] Maciag A E, et al. Abstract ND07: BBO-8520, a first-in-class, direct inhibitor of KRASG12C (ON), locks GTP-bound KRASG12C in the state 1 conformation resulting in rapid and complete blockade of effector binding[J]. Cancer Research, 2024, 84(7_Supplement): ND07-ND07.
[2] Caughey B A, Strickler J H. Targeting KRAS-Mutated Gastrointestinal Malignancies with Small-Molecule Inhibitors: A New Generation of Breakthrough Therapies[J]. Drugs, 2024, 84(1): 27-44. |
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