KRAS was once a notorious 'undruggable target' over the past few decades. Most cancers driven by KRAS mutations lack corresponding targeted drugs. Now, this dilemma is finally expected to be broken!
Revolution Medicines recently announced the publication of two peer-reviewed research papers in Nature. Two original papers highlight the discovery and translational implications of RMC-7977, a RAS(ON) multi-selective tri-complex inhibitor that exhibits unprecedented anti-tumor activity in preclinical models of RAS-mutant pancreatic ductal adenocarcinoma (PDAC). The first paper demonstrates RMC-7977 successfully targets signaling by both mutant and wild-type forms of RAS to drive potent and durable inhibition of RAS-mutated cancers. The second paper highlights the systematic evaluation of RMC-7977 in a wide range of preclinical models of PDAC. Oncogenic RAS proteins drive up to 30 percent of all human cancers, most notably non-small cell lung cancer (NSCLC), PDAC and colorectal cancer (CRC). RAS G12 mutations, such as G12D, G12V and G12C, predominate in human cancers. Approved KRAS-targeted cancer therapies target only one particular RAS mutation, KRAS G12C.
Chemenu has been working to develop more compounds for drug discovery. Here are the building blocks we can provide.