Pipeline
Inhibitors of kinase protein-protein interactions
PPI Pharmaceuticals is developing inhibitors of protein-protein interfaces on kinases involved in cancer. REPLACE turns peptidic binding determinants into small molecules aimed at sites outside the ATP pocket used by most kinase drugs.
The lead program is polo-box domain inhibitors of PLK1, obtained through REPLACE. A Phase I STTR, from May 2017 to November 2018, had two aims. Aim 1: lead optimization of PBD inhibitors obtained through REPLACE. Aim 2: phenotypic analysis, evaluation of drug-like properties, and anti-tumor effects, including determining in vivo activity in a prostate cancer model.
Two further programs are earlier. BRAF dimerization-interface inhibitors are being designed as capped macrocycles from peptidic leads, motivated by resistance after first-generation ATP-site BRAF drugs. Cyclin-groove inhibitors apply REPLACE to protein-protein contacts that advance the cell cycle in tumor cells.