LIM Kinase (LIMK) Degrader

THNAN69 is a PROTAC degrader targeting LIMK2, which efficiently degrades ectopically expressed EGFP-LIMK2 in live HuCCT1 cells with a DC₅₀ of 1 nM. THNAN69 induces isoform-specific ubiquitin-mediated degradation of LIMK2 by recruiting the CRBN E3 ligase, forming a stable ternary complex with LIMK2 and CRBN; this degradation process depends on the activity of cullin-RING ligase. THNAN69 does not reduce phosphorylated cofilin levels, as LIMK1 can compensate for the loss of LIMK2; it also stimulates compensatory activation of the Rho signaling pathway including PAK1/2 and ROCK1/2. THNAN69 serves as a selective chemical probe for dissecting the LIMK2 isoform-dependent biological mechanisms. THNAN69 can be used in the research of cholangiocellular carcinoma and acute lymphoblastic leukemia.

DD-03-156 ((S,R,S)-AHPC-Me-PEG2-dabrafenib) is a VHL-based PROTAC degrader targeting CDK17 and LIMK2. DD-03-156 serves as an excellent lead-like starting point for the development of selective chemical probes targeting CDK17 degradation.

DB0662 is a multi-target kinase-directed PROTAC degrader, targeting kinases including PTK2B, MAPK9, BLK, CSK, LIMK1, etc.