There is currently a resurgence of interest in developing covalent drugs due to the high potency, good selectivity, and prolonged effects which may results in less-frequent drug dosing and wider therapeutic windows for patients. BridGene Biosciences established a novel IMTACTM (Isobaric Mass Tagged Affinity Characterization) platform for covalent drug discovery. Using IMTACTM platform, an intelligently designed drug-like probe with alkyne tag is able to “fish out” and identify proteins covalently bound to probes from live cells which enables us to discover druggable opportunities across the entire proteome. There are several advantages of IMTACTM : 1. Discover ligands for unliganded or undruggable targets; 2. Reduce the time and cost of lead discovery; 3. Identify additional targets of drugs or clinical candidates; 4. Build ligand-target interaction database and guide drug design. Using IMTACTM platform, our covalent library is screened in various live cells including cancer immune, and neuronal cell lines. The hit rate of IMTAC screening is about 20%, and the targets discovered by IMTACTM includes GMPS, Rictor, BTK, FABP5, ALDH, FUS, MIF and etc. Given the drug-like probe design, the probes can have nanomolar potency on the targets. And the drug like probe design minimizes the SAR efforts of developing a hit to a drug. IMTACTM platform allows us to expand the therapeutic applications of small molecule drugs to a new horizon.

Citation Format: Heather Ha, Robert Stanley, Qian Cai, Wendy Zhou, Hang Chen, Irene Yuan, Ping Cao. Small molecule covalent drug discovery by IMTACTM [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A136. doi:10.1158/1535-7163.TARG-19-A136