CDKL3 inhibitor HZ1 (C3I-22) is a first-in-class, specific inhibitor of CDKL3 (Cyclin-dependent kinase like 3) inhibitor with Kd of 5.16 uM, blocks CDKL3 mediated cell cycle progression both in vitro and in vivo
C3I-22 (HZ1) exhibits potent tumor-suppressing effect with IC50 of 0.348 and 0.086 uM in U2OS and DLD-1 cells respectively.
C3I-22 (HZ1) antagonizes cancer growth via cell cycle arrest in multiple models, reduces the levels of pRb and CDK4.
C3I-22 (HZ1) could overcome the acquired drug resistance of CDK4/6 inhibitor in ER+ breast cancer.
C3I-22 (HZ1) could act on a different stage (G0-to-G1 transition) from CDK4/6 inhibitor and meanwhile suppress the elevated CDK4/6 protein level.
C3I-22 significantly reduced the tumor number and volume, efficiently clear the tumor burden derived from the colon cancer patient.
CDKL3 belongs to Cyclin-Dependent Kinase Like (CDKL) kinase subfamily, which is part of CMGC Ser/Thr protein kinase superfamily. Serine/Threonine kinase, CDKL3 (Cyclin-dependent kinase like 3), crucially drives the rapid cell cycle progression and cell growth in cancers.