(S,R,S)-BBO-11818 

(S,R,S)-BBO-11818 is an orally active, highly selective (relative to NRAS and HRAS), non-covalent pan-KRAS inhibitor (IC₅₀=28-120 nM). (S,R,S)-BBO-11818 specifically binds to the Switch-II/Helix 3 pocket, disrupts the KRAS:RAF1 interaction by inducing conformational changes, and blocks the MAPK signaling pathway. (S,R,S)-BBO-11818 exhibits significant anti-tumor activity, which not only inhibits cell proliferation and induces apoptosis, but also drives tumor regression in xenograft models. (S,R,S)-BBO-11818 produces synergistic effects when combined with Cetuximab (HY-P9905), anti-PD-1 antibody or PI3Kα inhibitor. (S,R,S)-BBO-11818 is used in the research of KRAS mutation-related malignancies such as pancreatic cancer, non-small cell lung cancer and colorectal cancer^[1][2].

(S,R,S)-BBO-11818 (2.5 nM; 21 d) inhibits the long-term clonogenic growth of Capan-2 PDAC (KRAS^G12V) cells^[1].
(S,R,S)-BBO-11818 (3 nM; 15 d) inhibits the long-term clonogenic growth of LS513 colorectal cancer (KRAS^G12D) cells^[1].
(S,R,S)-BBO-11818 (30 nM; 4 h) potently and selectively inhibits SOS-mediated nucleotide exchange of KRAS (wild-type and oncogenic mutants), including the constitutively GTP-bound KRAS^A59G mutant, but shows no activity against NRAS^[2].
(S,R,S)-BBO-11818 (0.1-200 nM; 96 h) potently inhibits the viability of Ba/F3 cells driven by wild-type or oncogenic KRAS mutants, including the constitutively GTP-bound KRAS^A59G, while its activity is reduced in KRAS^G12R and KRAS^Q61X mutants^[2].
(S,R,S)-BBO-11818 (0-0.1 μM; 72 h & 96 h) potently and selectively inhibits 3D spheroid growth of human cancer cell lines driven by oncogenic KRAS mutations or KRAS amplification, while exhibiting extremely low activity in non-KRAS-driven cell lines^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

(S,R,S)-BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induces potent and statistically significant tumor growth inhibition and tumor regression in KRAS^G12D-mutant HPAC pancreatic cancer CDX models^[1].
(S,R,S)-BBO-11818 (10-100 mg/kg; p.o.; BID; 28 d) induces potent, dose-dependent, and statistically significant tumor growth inhibition in the KRAS^G12V-mutant H441 non-small cell lung cancer CDX model^[1].
(S,R,S)-BBO-11818 (100 mg/kg; p.o.; BID) induces a statistically significant reduction in tumor cell proliferation and promotes an increase in apoptosis levels in the KRAS^G12V-mutant Capan-2 pancreatic cancer CDX model^[1].
(S,R,S)-BBO-11818 (10-100 mg/kg; p.o.; single administration) exerts dose- and time-dependent inhibition of pERK and DUSP6 in KRAS^G12D pancreatic ductal adenocarcinoma (PDAC) xenografts, with an in vivo EC₅₀ of 138 nmol/L for pERK inhibition; pERK levels are reduced by up to 85% following a single oral dose of 100 mg/kg^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

733.73

C₃₄H₃₃F₆N₇O₃S

3029184-80-0

CCN([C@@H]1CN(CC1)C(OC)=O)C2=NC(OC[C@@]34N(CCC4)C[C@@H](C3)F)=NC5=C2C=C(C(F)(F)F)C(C6=C7C(SC(N)=C7C#N)=C(C=C6)F)=C5F

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Zuhui ZHANG, et al. Compositions and methods for inhibition of kras. WO2024030633A1. 2023.