Selectively Targeting Tropomyosin Receptor Kinase A (TRKA) via PROTACs
Weiguo Xiang, Shaomeng Wang
Abstract
Tropomyosin receptor kinases (TRKs) are promising cancer therapeutic targets. Chen ( J. Med. Chem. 2020, DOI: 10.1021/acs.jmedchem.0c01342) report the discovery of CG416 and CG428 as two potent small-molecule proteolysis-targeting chimera (PROTAC) degraders selective for TRKA over TRKB and TRKC. CG416 and CG428 are valuable research tool compounds for in vitro and in vivo studies and promising lead compounds for further optimization.
Topics & Concepts
Tropomyosin receptor kinase AChemistryTropomyosin receptor kinase BTropomyosinTrk receptorKinaseTropomyosin receptor kinase CIn vivoNeurotrophinLow-affinity nerve growth factor receptorReceptorPharmacologyBiochemistryNeurotrophic factorsBiologyGrowth factorBiotechnologyMyosinPlatelet-derived growth factor receptorProtein Degradation and InhibitorsUbiquitin and proteasome pathwaysPeptidase Inhibition and Analysis