C3TD879 is a potent, selective first-in-class Citron kinase (CITK) chemical inhibitor with biochemical IC50 of 12 nM.
C3TD879 is highly selective for CITK in the Eurofins KinaseProfiler assay against 373 human kinases, with exception of NEK family kinases AAK1 and BIKE (>17-fold selective).
C3TD879 directly binds to and stabilizes CITK kinase domain (Met1-Ala449) in target engagement assays, binds to NL-CITK KD with Kd = 0.3 nM and to full-length NL-CITK with Kd = 9.5 nM.
C3TD879 shows no on-target antiproliferative phenotype in HeLa cells.
C3TD879 does not significantly affect cell cycle progression or induce multinucleation in HeLa cells.
C3TD879 is the first chemical probe suitable for interrogating the complex biology of CITK.
CITK is an AGC-family serine/threonine kinase closely related to the Rho-associated (ROCK) and Aurora (AURK) protein kinases, has been reported to play both catalytic and structural roles during cytokinesis.