N-(3-(5-(2-cyclopropylpyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,6-difluorophenyl)propane-1-sulfonamide

HRX-0233 is a small-molecule MAP2K4 inhibitor. HRX-0233 results in strong tumor shrinkage without any apparent toxicity in H358 KRASG12C-mutant non-small cell lung cancers (NSCLC) in vivo. HRX-0233 efficiently prevents feedback activation of receptor tyrosine kinases (RTKs) upon monotherapy KRAS inhibitor Sotorasib (HY-114277) and causes a more sustained and complete inhibition of MAPK signaling. HRX-0233 is promising for research of AR-negative prostate cancer, lung and colon cancers[1][2].

[1] Jansen RA, et al. Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors in KRAS-mutant cancers. Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2319492121. DOI:10.1073/pnas.2319492121
[2] Tipayasri P. Development of Rational Combination Therapies for Patients with Metastatic Prostate Cancer and Loss of the PTEN Tumor Suppressor Gene[D]. , 2024.