GP-82996 (CINK4) is a pharmacological inhibitor specifically targeting CDK4/6, exhibiting IC50 values of 1.5 μM for CDK4/cyclin D1, 5.6 μM for CDK6/cyclin D1, and 25 μM for Cdk5/p35. It effectively induces apoptosis in U2OS cancer cells, positioning it as a potential investigational tool in cancer research [1] [2].

Cdk4/cyclin D1:1.5 μM, CDK5-p35:25 μM, V-abl:>10 μM, CDK6-CyclinD1:5.6 μM, c-Met:>10 μM, Insulin Receptor:>10 μM, CDK6-CyclinD2:>50 μM, CDK2-CyclinE:>50 μM, IGF-1R:>10 μM, CDK2/cyclinA:>50 μM, CDK1/cyclinB:>100 μM, CDK4/Cyclin D2:>50 μM

GP-82996 (5, 10 μM; 24 hours) induces G1 arrest and G0-G1/S ratio increase in U2OS (p16 negative) and MRC-5 (p16 positive) cells [1]. GP-82996 (5, 10 μM; 24 hours) reduces hyperphosphorylation of pRb, but has no effect on CDK4 levels in U2OS, MRC-5 cells [1]. GP-82996 (5, 10 μM; 48 hours) induces aooptosis in 83% of U2OS cells in concentration of 10μM [1]. GP-82996 (0.1-40 μM; 24,48, 72 hours) inhibits the cell proliferation of A549, H358, SKLU-1, H23, PC14 cells with IC 50 values of 72 h are 4-7 μM [2]. GP-82996 (3, 5, 10 μM; 48 hours) induces G1 arrest in A549 and H23 cells [2]. GP-82996 ((1, 3, 5, 10 μM; 72 hours) enhances Paclitaxel sensitivity in KRAS mutation-bearing lung cancer cells (A549, SKLU-1, H23 cells) [2]. GP-82996 (10 μM; 72 hours) combined with Paclitaxel (3 nM; 72 hours) increases the apoptosis of A549 and H23 cells [2].

GP-82996 (30 mg/kg, i.p. for 29 days) exhibits smaller final tumor volume compared with vehicle control in mouse xenograft models [1]. Animal Model: 19-21 g female BALB/c nu/nu mice xenograft model (HCT116 tumors volume=100 mm 3 ) [1] Dosage: 30 mg/kg Administration: i.p. every 12 hours for 29 days Result: Showed smaller final tumor volume compared with vehicle control in mouse xenograft models.