SHR1127

SHR1127 is an orally bioavailable, highly potent, and selective small molecule inhibitor of the KRAS G12D mutant protein, developed by Shanghai Hengrui Pharmaceutical. KRAS G12D is a prevalent oncogenic driver in several solid tumors, including pancreatic, colorectal, and non-small cell lung cancers. SHR1127 exhibits picomolar binding affinity to the GDP-loaded form of KRAS G12D and effectively suppresses downstream signaling, such as ERK phosphorylation, leading to significant anti-proliferative activity in mutant cell lines. Preclinical studies have demonstrated robust tumor regression in xenograft models and a favorable safety profile with a wide therapeutic window. As of early 2024, the program was transitioning toward clinical evaluation with a planned Investigational New Drug (IND) submission.