cdk4/6 in 2

CDK4 6-IN-2 is a potent inhibitor of CDK4 and CDK6 [IC50s: 2.7 and 16 nM].

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].

AZD8421 is a potent and highly selective inhibitor of cyclin-dependent kinase 2 (CDK2) with an IC50 of 9nM, demonstrating greater selectivity over CDK1, CDK4, and CDK6. This compound also exhibits antiproliferative properties by effectively inhibiting Rb phosphorylation. In models of breast and ovarian cancer, AZD8421 has shown significant activity both as a monotherapy and in combination with CDK4 6 inhibitors.

LSN3106729 hydrochloride, the metabolite of Abemaciclib , is a CDK inhibitor with antitumor activity. LSN3106729 hydrochloride and a CRBN ligand have been used to design PROTAC CDK4 6 degrader[1]. [1]. Edward S. Kim, et al. Abemaciclib in Combination with Single-Agent Options in Patients with Stage IV Non-Small Cell Lung Cancer: A Phase Ib Study. [2]. Nathanael Gray, et al. Degradation of cyclin-dependent kinase 4 6 (cdk4 6) by conjugation of cdk4 6 inhibitors with e3 ligase ligand and methods of use. WO2017185031A1.

CDK HDAC-IN-2 is a potent dual HDAC CDK inhibitor that acts on HDAC1 (IC50: 6.4 nM), HDAC2 (IC50: 0.25 nM), HDAC3 (IC50: 45 nM), HDAC6 and 8 (IC50 > 1000 nM), CDK1 (IC50: 8.63 nM), CDK2 (IC50: 0.30 nM), and CDK4, 6, and 7 (IC50 > 1000 nM). CDK HDAC-IN-2 can arrest the cell cycle in the G2 M phase and induce apoptosis, demonstrating excellent anti-proliferative and significant anti-tumor effects.

CDK4 6-IN-14 is a potent, highly selective inhibitor of Cyclin-Dependent Kinases 4 and 6 (CDK4 6), with inhibition concentrations (IC50s) of 10 nM and 16 nM, respectively. It shows over 60-fold selectivity for CDK4 6 compared to CDKs 1, 2, 7, and 9, and exhibits significant selectivity against 205 other kinases.

CDK4 6-IN-17 (compound 12) is an orally bioavailable inhibitor of CDK4 6, exhibiting potent activity with IC50 values between 10-100 nM in BE(2) cells, and has demonstrated efficacy in inhibiting tumor growth in the COLO205 xenograft model [1].

MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell lines. It demonstrates robust suppression of the MAPK pathway (EGFR WT IC50 = 281 nM, c-MET IC50 = 205 nM, B-RAF WT IC50 = 112 nM, CDK4 6 IC50 = 95 and 184 nM, respectively) and exhibits pronounced activity against mutated forms of EGFR and B-RAF (EGFR T790M IC50 = 69 nM and B-RAF V600E IC50 = 83 nM) [1].