CDK2 degrader 3 is a selective CDK2 molecular glue-like degrader. CDK2 degrader 3 induces G1 cell cycle arrest in CCNE1-amplified cancer cells. CDK2 degrader 3 is applicable to breast cancer-related research [1].
In Vitro, CDK2 degrader 3 (compound 1) preferentially forms ternary complexes with CDK2/CCNE1 over CDK1/CCNB1[1]. CDK2 degrader 3 drives preferential ubiquitination of CDK2/cyclin E1 over CDK1/cyclin B1[1]. CDK2 degrader 3 (24 h) potently degrades CDK2 in TOV21G cells with high selectivity over CDK1 and CDK9, with an absDC50 of 8 nM[1]. CDK2 degrader 3 (14 h) potently degrades CDK2 in MKN1 CCNE1amp cells with 95% maximum degradation at an absDC50 of 11 nM[1]. CDK2 degrader 3 (14 h) potently degrades CDK2 in HCC1569 CCNE1amp cells with 94% maximum degradation at an absDC50 of 10 nM[1]. CDK2 degrader 3 (24 h) potently inhibits RB phosphorylation at S807/811 in MKN1 CCNE1amp cells with 96% maximum inhibition at an absIC50 of 27 nM[1]. CDK2 degrader 3 (24 h) inhibits RB phosphorylation at S807/811 in HCC1569 CCNE1amp cells with 87% maximum inhibition at an absIC50 of 34 nM[1]. CDK2 degrader 3 (7 day) potently inhibits proliferation in CCNE1amp cancer cells with significantly lower activity in CCNE1non-amp TOV21G cells, with relIC50 values of 7 nM (MKN1), 16 nM (HCC1569), 28 nM (OVCAR3), and 4000 nM (TOV21G)[1]. CDK2 degrader 3 (500 nM (10x DC90); 24 h) selectively degrades CDK2 in human PBMCs with minimal off-target protein modulation[1]. CDK2 degrader 3 (80 nM; 24 h) suppresses E2F target gene expression in MKN1 cells[1]. CDK2 degrader 3 (1 μM Palbociclib (co-treatment); 24 h) co-degrades CDK2 and cyclin E1 in Palbociclib-adapted MCF7 and Hs578t breast cancer cells[1].
References:
[1]. Kwiatkowski N, et al. CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers. Cell Chem Biol. 2025;32(4):556-569.e24.
In Vitro, CDK2 degrader 3 (compound 1) preferentially forms ternary complexes with CDK2/CCNE1 over CDK1/CCNB1[1]. CDK2 degrader 3 drives preferential ubiquitination of CDK2/cyclin E1 over CDK1/cyclin B1[1]. CDK2 degrader 3 (24 h) potently degrades CDK2 in TOV21G cells with high selectivity over CDK1 and CDK9, with an absDC50 of 8 nM[1]. CDK2 degrader 3 (14 h) potently degrades CDK2 in MKN1 CCNE1amp cells with 95% maximum degradation at an absDC50 of 11 nM[1]. CDK2 degrader 3 (14 h) potently degrades CDK2 in HCC1569 CCNE1amp cells with 94% maximum degradation at an absDC50 of 10 nM[1]. CDK2 degrader 3 (24 h) potently inhibits RB phosphorylation at S807/811 in MKN1 CCNE1amp cells with 96% maximum inhibition at an absIC50 of 27 nM[1]. CDK2 degrader 3 (24 h) inhibits RB phosphorylation at S807/811 in HCC1569 CCNE1amp cells with 87% maximum inhibition at an absIC50 of 34 nM[1]. CDK2 degrader 3 (7 day) potently inhibits proliferation in CCNE1amp cancer cells with significantly lower activity in CCNE1non-amp TOV21G cells, with relIC50 values of 7 nM (MKN1), 16 nM (HCC1569), 28 nM (OVCAR3), and 4000 nM (TOV21G)[1]. CDK2 degrader 3 (500 nM (10x DC90); 24 h) selectively degrades CDK2 in human PBMCs with minimal off-target protein modulation[1]. CDK2 degrader 3 (80 nM; 24 h) suppresses E2F target gene expression in MKN1 cells[1]. CDK2 degrader 3 (1 μM Palbociclib (co-treatment); 24 h) co-degrades CDK2 and cyclin E1 in Palbociclib-adapted MCF7 and Hs578t breast cancer cells[1].
References:
[1]. Kwiatkowski N, et al. CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers. Cell Chem Biol. 2025;32(4):556-569.e24.