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CDK2 participates in regulating cell cycle and a range of physiological and pathological processes. Excessive expression of cyclin E occurs in many types of cancer, including breast, lung, colorectal, gastric, and bone cancers, as well as in leukemia and lymphoma, which is a major protein binding partner of CDK2. These indicated that CDK2 and its cyclin binding partners are potential anti-cancer targets and in pre-clinical experiments, CDK2-targeted therapeutics exhibited success in limiting tumor growth, besides, it has ability to reduce side effects of current chemotherapy drugs.
Cyclin-dependent kinase 2 (CDK2), also known as cell division protein kinase 2, belongs to the cyclin-dependent kinase family of Ser/Thr protein kinases. It is encoded by the CDK2 gene. CDK2 is a catalytic subunit of the cyclin-dependent kinase complex, whose activity is restricted to the G1-S phase in the cell cycle, where cells make proteins necessary for mitosis and replicate their DNA.
The studies indicated that for normally functioning tissue, there is little effect of the deletion of CDK2. In CDK2-deletion mice model, they remained viable, while the mice was thinner than wild mice, and meiotic function of both male and female mice was inhibited, which suggested that CDK2 is not necessary for the cell cycle of healthy cells but is essential for meiosis and reproduction. Reletive studies indicated that CDK1 is supposed to have ablity to compensate for many aspects of Cdk2 deletion (except for meiotic function).
CDK2 is a G1-S phase checkpoint control, due to it is active during G1 and S phase of the cell cycle. CDK2 initiates the transcription of genes needed for cell cycle progression and regulates the phosphorylation of other regulatory proteins to link other processes to cell cycle progression. Besides, CDK2 plays a pivotal part in cell cycle regulation and is involved in many biological processes, such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation.
Although the deletion of CDK2 has no significant effect on normally functioning cells, it is important for cancer cells. CDK2 regulates cancer cells process through different ways. On the one hand, the inhibition of CDK2 forced Myc/Ras expressing cells into cellular senescence, thereby inhibits their enhancement on cancer process. On the other hand, CDK2 plays dual roles in DNA damage and DNA damage response. CDK2 is activated when DNA is damaged by internal or external genotoxic stresses and its activation are necessary for triggering DDR, while CDK2 inactivation directly results in DNA damage and activation of DDR.
Approved Drugs
Bosutinib, trilaciclib, etc.
Drugs in Development
Staurosporine, olomoucine, 2-Amino-6-Chloropyrazine, 6-O-Cyclohexylmethyl Guanine, etc.
Multiple Receptor Tyrosine Kinases Inhibitor
Bosutinib
B-Raf inhibitors, heat shock protein 90 inhibitors plus dinaciclib were shown to be highly effective in melanoma cell lines that had acquired or intrinsic resistance to BRAF and Hsp90 inhibition.
CDK2 TestingCD BioSciences provides CDK2 testing services by WB, IP, IHC or IF assay. The results of CDK2 testing are used to evaluate the activities of candidates against CDK2 or targeted diseases. You can choose one or more testing ways to detect the level of CDK2 according to your experiment.
Hit Identification (show more)The goal of early drug discovery is to find novel lead compounds that have the desired potency, selectivity, and ADMET properties for pre-clinical evaluation.
CD BioSciences offers hit identification services to make your find targeted compounds more successful and faster.
Pharmacological Experiments (show more)We will make a specific experimental plan according to your requirements, including but not limited to
Cancers Models Screening (show more)We will make specific cancer models to accelerate your targeted drug discovery project, including but not limited to
CD BioSciences will establish the specific cancer model according to your requirements to evaluate the inhibitory activity of your candidates targeted CDK2. We have various cell lines and the species of our animal models cover rats, mice, rabbits, dogs, and non-human primates.
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