CDK4/6-IN-6

Abemaciclib metabolite M20 (CDK4/6-IN-4) is an active metabolite of Abemaciclib. Abemaciclib metabolite M20 is a selective CDK4/6 inhibitor and can be used for researches on the treatment of cancer.

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].

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

CDK4/6-IN-3, a brain-penetrant CDK4/CDK6 inhibitor (Kis: <0.3 nM and 2.2 nM), is used for the treatment of glioblastoma and inhibits CDK1 with a Ki of 110 nM.

Lerociclib (G1T38) is a selective and highly potent CDK4/6 inhibitor with anticancer and antitumor activity, inhibits CDK4/CyclinD1 and CDK6/CyclinD3, and inhibits tumor growth in an animal model of endocrine-resistant breast cancer. Due to the poor solubility, for animal studies, the salt form T11345L is recommended.

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.

CDK4/6-IN-23 (Compound 42) is a potent and selective inhibitor of CDK4/6, displaying an IC50 of 11 nM for CDK6. This compound significantly activates immune cells and enhances IL-3 production. In mice undergoing 5-FU chemotherapy, CDK4/6-IN-23 demonstrates dual bone marrow protection and immunomodulatory effects.

CDK4/6/HDAC-IN-1 (Compound N14) is a dual-target inhibitor of CDK4/6 and HDAC, with IC50 values of 7.23 nM for CDK4, 13.20 nM for CDK6, 55.66 nM for HDAC1, and 48.38 nM for HDAC6. It induces apoptosis and G0/G1 phase arrest through the HDAC-p21-CDK signaling pathway and can inhibit hepatocellular carcinoma.

CDK4/6-IN-24 (Compound A) is an inhibitor of CDK4/6 with broad-spectrum antitumor activity. It can effectively inhibit various cancer cells, exhibiting an IC50 in the submicromolar range.

CDK4/6/BRD4-IN-1 (B15) is an inhibitor targeting CDK4, CDK6, and BRD4, with IC50 values of 220 nM for BRD4-BD2, 146 nM for BRD4-BD1, 106 nM for CDK6, and 85 nM for CDK4. This compound is applicable for research in non-small cell lung cancer (NSCLC) and can induce cell cycle arrest and apoptosis.

LEQ803 (N-DesmethylRibociclib) is a metabolite of the CDK4/6 inhibitor Ribociclib, produced through metabolism by CYP3A4. This compound holds potential applications in the field of oncology.

LA-CB1 is a derivative of Abemaciclib that targets CDK4/6 and promotes their degradation via the ubiquitin-proteasome pathway, thereby blocking the CDK4/6-Cyclin D1-Rb-E2F axis and inducing G0/G1 cell cycle arrest and apoptosis (Apoptosis). It demonstrates antiproliferative activity against MDA-MB-231 cells with an IC50 of 0.27 µM and effectively inhibits epithelial-mesenchymal transition, cell migration, invasion, and angiogenesis. In highly invasive models like triple-negative breast cancer (TNBC), LA-CB1 significantly suppresses tumor growth, showing robust dose-dependent antitumor activity. This compound can be utilized in breast cancer research.

CDK4/6-IN-15 hydrochloride is an orally active selective inhibitor of CDK4/6. It effectively restrains the growth of cancer cells by arresting the cell cycle at the G1 phase. Additionally, CDK4/6-IN-15 hydrochloride inhibits phosphorylation of the retinoblastoma tumor suppressor protein (Rb) at site S780 and suppresses E2 factor (E2F)-regulated gene expression.

LO-3-63 is a Ribociclib analogue featuring a truncated fumaramide group and acts as a CDK4/6 degrader with PROTAC properties. It degrades CDK4/6 in cells via a CUL4DCAF16-dependent pathway.

Selective Cdk4 degrader. Degrades Cdk4 in Molt-4 cells, with no effect on Cdk6 levels. Displays cereblon-dependent degradation. Jiang et al (2019) Development of dual and selective degraders of cyclin-dependent kinases 4 and 6. Angew.Chem.Int.Ed.Engl. 58 6321 PMID:30802347

XY028-140 is a selective CDK4/CDK6 degrade and inhibits both CDK4/6 expression and activity in cancer cells. XY028-140 is a PROTAC connected by ligands for Cereblon and CDK.

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.

CDK4/6-IN-5 is a highly effective inhibitor of CDK4 and CDK6, with Ki values of 0.2 nM for CDK4/Cyclin D1 and 4.4 nM for CDK6/Cyclin D3 (WO2019207463A1, example A93).

CDK4/6-IN-12 is a potent cyclin-dependent kinase 4/6 (CDK4/6) inhibitor with enzymatic inhibitory activity against CDK4 and CDK6, having IC50 values of 592.3 nM and 3090 nM, respectively. CDK4/6-IN-12 can be used in cancer research[1].

CDK4/6-IN-7, a highly potent and selective orally active inhibitor of CDK4/6, demonstrates impressive inhibition activity with IC50 values of 1.58 nM and 4.09 nM respectively. This compound is particularly valuable for breast cancer research [1].

CDK4/6-IN-8 (Compound 7p) is a selective inhibitor of CDK4 with an IC50 of 5.01 nM and CDK6 with an IC50 of 3.97 nM.

CDK4/6-IN-9 (compound 10) is a selective inhibitor of CDK4/6, demonstrating activity on CDK6/cyclin D1 (IC50: 905 nM), and holds potential research value in multiple myeloma (MM).

Dalpiciclib (SHR-6390) hydrochloride is a highly selective, orally active CDK4/6 inhibitor with IC50 values of 12.4 nM and 9.9 nM, respectively, acting as an antitumor agent in breast and esophageal squamous cell carcinomas.

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.