CDK2-IN-31 is a CCNE1:CDK2 complex inhibitor with an IC50 of 0.13 μM. CDK2-IN-31 binds to a cryptic allosteric pocket at the CCNE1:CDK2 interface, inducing structural rearrangements of the CDK2 A-loop that disrupt the kinase's active conformation and interfere with substrate binding. CDK2-IN-31 inhibits phosphorylation of retinoblastoma protein 1 (RB1) in CCNE1 -dependent ovarian cancer cells. CDK2-IN-31 impairs coenrichment of protein PRC1 with CCNE1-N112C:CDK2 complexes. CDK2-IN-31 can be used for the research of ovarian cancer [1].
In Vitro, CDK2-IN-31 (Compound I-125A) (2 h) inhibits kinase activity of mutant CCNE1-N112C:CDK2 and WT CCNE1:CDK2 complexes, with IC50 values ranging from 0.10-0.36 μM[1]. CDK2-IN-31 (1 nM-20 μM; 1 h) engages CCNE1-N112C:CDK2 complexes in intact HEK293T cells with a TE50 of 1.0 μM[1]. CDK2-IN-31 (0.01-20 μM; 1 h) binds endogenous WT CCNE1 in OVCAR3 cells, increasing its thermal stability with a TE50 of 0.9 μM[1]. CDK2-IN-31 (0.01-20 μM; 48 h) inhibits RB1 phosphorylation in CCNE1-dependent OVCAR3 cells with an IC50 of 0.33 μM, but has no effect in CCNE1-independent 22Rv1 cells[1].
References:
[1]. Zhang Y, et al. An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes. Nat Chem Biol. 2025;21(3):420-431.
In Vitro, CDK2-IN-31 (Compound I-125A) (2 h) inhibits kinase activity of mutant CCNE1-N112C:CDK2 and WT CCNE1:CDK2 complexes, with IC50 values ranging from 0.10-0.36 μM[1]. CDK2-IN-31 (1 nM-20 μM; 1 h) engages CCNE1-N112C:CDK2 complexes in intact HEK293T cells with a TE50 of 1.0 μM[1]. CDK2-IN-31 (0.01-20 μM; 1 h) binds endogenous WT CCNE1 in OVCAR3 cells, increasing its thermal stability with a TE50 of 0.9 μM[1]. CDK2-IN-31 (0.01-20 μM; 48 h) inhibits RB1 phosphorylation in CCNE1-dependent OVCAR3 cells with an IC50 of 0.33 μM, but has no effect in CCNE1-independent 22Rv1 cells[1].
References:
[1]. Zhang Y, et al. An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes. Nat Chem Biol. 2025;21(3):420-431.