cdk in 2

CDK-IN-2 (CDK inhibitor II) is a potent and specific CDK9 inhibitor (IC50: <8 nM).

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.

CDK9-IN-2 is a specific CDK9 inhibitor with an IC50 of 5 nM in the A2058 skin cell line (72 hours) and 7 nM in the H929 multiple myeloma cell line (72 hours).

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

CDK2-IN-4 is a potent and selective inhibitor of CDK2 with an IC50 of 44 nM for CDK2/cyclin A. It shows 2,000-fold selectivity over CDK1/cyclin B with IC50 of 86 uM.

CDK-IN-14 (B34) is a CDK2 inhibitor (IC50=0.097 μM) that exhibits anti-hepatocellular carcinoma activity. It inhibits the cell cycle in HepG-2 cancer cells and induces apoptosis (apoptosis) through a caspase-mediated mechanism.

Protein kinase inhibitor 11 (Compound I-96) is an agent that inhibits the activity of PIM-1, CDK-2, GSK-3, and SRC. It shows potential for research in cancer, autoimmune diseases, and neurodegenerative disorders.

Apoptosisinducer 18 is an effective apoptosis-inducing agent that exhibits significant cytotoxicity against the breast cancer cell line MCF-7 (IC50 = 0.559 μM). It induces apoptosis by binding to DNA and causing damage, as well as interacting with the active site of CDK-2, which disrupts kinase activity, thereby impeding cell cycle progression. This compound can be utilized in breast cancer research.

Amsilarotene (TAC101) inhibits the phosphorylation of retinoblastoma gene product (RB) and increases the presence of 2 cyclin-dependent kinases (CDK) inhibitors resulting in cell cycle arrest. This agent also causes a cytotoxic decline in the thymidylate synthase and cyclin A expression.

GW8510 is a CDK2 (cell cycle protein-dependent kinase 2) inhibitor and RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) inhibitor that affects DNA synthesis and antiproliferation in tumor cells. In mammalian aging models, GW851 improves cognition and prolongs lifespan, which may be related to the modulation of the expression of cell cycle-related protein p21 and CDK family genes, as well as the improvement of mitochondrial function.

CKD-712 is a nuclear factor NF-kappa B inhibitor. CKD-712 suppressed MMP-9, but not MMP-2 and other NF-κB-regulated proteins involved in cancer metastasis such as VEGF. CKD-712 induced cell cycle arrest at G2M phase by suppressing cyclin A, cyclin B and C

Roccellic acid is a lichen secondary metabolite that has been found in R. montagnei and has antibacterial and anticancer activities.1,2 It is active against the bacteria S. gordonii and P. gingivalis (MIC = 46.9 μg/ml for both).1 Roccellic acid (100 μg/ml) inhibits proliferation of MDA-MB-231, MCF-7, and DLD-1 cancer cells by 65.3, 75.8, and 87.9%, respectively.2 |1. Sweidan, A., Chollet-Krugler, M., Sauvager, A., et al. Antibacterial activities of natural lichen compounds against Streptococcus gordonii and Porphyromonas gingivalis. Fitoterapia 121, 164-169 (2017).|2. Mishra, T., Shukla, S., Meena, S., et al. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it's in silico docking study against CDK-10. Rev. Bras. Farmacogn. 27(6), 724-728 (2017).

Potent and selective CLK inhibitor (IC50 values are 28, 88 and 510 nM for CLK4, 1 and 2, respectively). Exhibits no significant activity at CLK3, DYRK, CDK or GSK3 at a concentration of 10 μM. Inhibits growth of a range of cancer cell lines in vitro at subnanomolar concentrations. Walter et al (2018) Molecular structures of cdc2-like kinases in complex with a new inhibitor chemotype. PLoS One 13 e0196761 PMID:29723265

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.

6-Chloro-2-fluoropurine is a heterocyclic building block.1,2It has been used in the synthesis of purine nucleosides that inhibit cyclin-dependent kinases (CDKs)in vitro.16-Chloro-2-fluoropurine has also been used in the synthesis of purine nucleosides that are active against HIV-1 and hepatitis B virus (HBV)in vitro.2 1.Wilson, S.C., Atrash, B., Barlow, C., et al.Design, synthesis and biological evaluation of 6-pyridylmethylaminopurines as CDK inhibitorsBioorg. Med. Chem.19(22)6949-6965(2011) 2.Lee, K., Choi, Y., Gullen, E., et al.Synthesis and anti-HIV and anti-HBV activities of 2'-fluoro-2',3'-unsaturated L-nucleosidesJ. Med. Chem.42(7)1320-1328(1999)

CDK7-IN-2 hydrochloride hydrate (Example 6) is a potent and specific inhibitor of the CDK7 enzyme, exhibiting significant anti-cancer properties.

CDK2-IN-7 is a CDK2 inhibitor for treating cancer (IC50 < 50 nM).

3-Methylthienyl-carbonyl-JNJ-7706621 is a highly potent and selective inhibitor of cyclin-dependent kinase (CDK), showing IC50 values of 6.4 nM for CDK1/cyclin B and 2 nM for CDK2/cyclin A. It also exhibits potent inhibition of GSK-3 (IC50 = 0.041 μM) and moderate inhibition of CDK4, VEGF-R2, and FGF-R2 (IC50 = 0.11 μM, 0.13 μM, and 0.22 μM, respectively), making it significant for cancer research.

CDK1/2/4-IN-1 (compound 3a) is a potent CDK inhibitor with IC50 values of 1.47, 0.78, and 0.87 μM for CDK1, CDK2, and CDK4, respectively. It can be used in cancer research to arrest the cell cycle at the G2/M phase and induce apoptosis, elevating Bax, caspase-3, and P53 levels while decreasing Bcl-2 levels [1].

Riviciclib hydrochloride (P276-00) is a novel inhibitor of CDK1, CDK4, and CDK9, with IC50 values of 79 nM, 63 nM, and 20 nM, respectively, currently in Phase 2/3.

VMY-1-103 is a potent CDK inhibitor, is also a novel dansylated analog of purvalanol B, was shown to inhibit cell cycle progression and proliferation in prostate and breast cancer cells more effectively than purvalanol B. VMY-1-103 , but not purvalanol B, significantly decreased the proportion of cells in S phase and increased the proportion of cells in G(2) M. VMY-1-103 increased the sub G(1) fraction of apoptotic cells, induced PARP and caspase-3 cleavage and increased the levels of the Death Receptors DR4 and DR5, Bax and Bad while decreasing the number of viable cells, all supporting apoptosis as a mechanism of cell death. VMY-1-103 possesses unique antiproliferative capabilities and that this compound may form the basis of a new candidate drug to treat medulloblastoma.

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.

THZ2 (CDK7-IN-1), an analog of THZ1, is a potent and selective CDK7 inhibitor(IC50:13.9 nM),with the potential to treat Triple-negative breast cancer (TNBC).

CDK2/Bcl2-IN-1 (compound 1) is a saponin-based inhibitor of CDK-2 (IC50=117.6 nM) with potent cytotoxic effects on cancer cells, also inhibiting Bcl-2 and promoting apoptosis in A549 lung cancer cells [1].