THNAN69

THNAN69 is a highly potent, selective, and cell-active proteolysis-targeting chimera (PROTAC) designed to degrade LIM domain kinase 2 (LIMK2). Developed by Goethe University Frankfurt and the Structural Genomics Consortium (SGC), THNAN69 consists of the dual LIMK1/2 inhibitor LIMKi3 linked to a cereblon (CRBN) E3 ligase ligand. It induces isoform-specific, ubiquitin-mediated degradation of LIMK2 with a half-maximal degradation concentration ($DC_{50}$) of 1 nM and near-complete depletion ($D_{max}$ of ~90%) at 10 nM, without affecting LIMK1 protein levels. As a high-quality chemical probe, THNAN69 serves as a valuable research tool to investigate the cellular roles of LIMK2 in actin cytoskeleton dynamics, cell motility, and diseases such as cancer (e.g., cholangiocarcinoma, acute lymphoblastic leukemia) and ocular diseases (e.g., glaucoma).

Other names

compound 22bcompound22bcompound-22b