PBI-381

PBI-381 is a potent and selective Proteolysis Targeting Chimera (PROTAC) designed to degrade the KRasG12D mutant protein. Developed by Polymed Biopharmaceuticals, it is intended for the treatment of solid tumors harboring the KRasG12D mutation, such as pancreatic, colorectal, and lung cancers. In preclinical studies, PBI-381 demonstrated high potency with a DC50 (degradation IC50) of less than 1 nM and a maximal degradation (Dmax) exceeding 98% in cancer cell lines. It has shown robust tumor regression in KRasG12D pancreatic cancer xenograft models (PK59) and exhibited superior anti-tumor activity and more favorable tissue distribution compared to other clinical-stage KRasG12D PROTACs like ASP3082. The compound is currently undergoing IND-enabling studies to progress toward clinical trials.

Other names

KRAS G12D PROTACKRAS G12D Degrader