Advanced development of human mutant IDH1 inhibitors (Chemical Biology Consortium/NCI Experimental Therapeutics Collaboration)

National Center For Advancing Translational Sciences

Investigators

Linked publications & trials

Abstract

This collaborative team - composed of groups from NCI, CBC/NExT, UNC and NCATS - aims to build on previous research by uncovering novel inhibitors of mutant IDH1 for anticancer indications. During this period, the team performed a number of advanced in vitro and in vivo studies, including multi-species pharmacokinetics analyses and a repeat dose toxicity assessment, on a series of lead molecules in preparation for preclinical studies. A lead molecule is also being evaluated for in vivo efficacy in a patient-derived xenograft model of mIDH1 cancer. Through our efforts, the team published a full, in vitro, biological profile comparison of a number of mIDH1 compounds which have been published in the literature, some of which are in the clinic. The team also published a second paper on the early stages of our medicinal chemistry structure activity studies.