China
Africa
Explore chapters and articles related to this topic
Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Cdk proteins regulate and control both the G1/S and the G2/M transition events and are considered responsible for all aspects of cell-cycle progression, but also require positive regulatory partners known as cyclins for their activity. Research has shown that all tumor cells have alterations to their machinery controlling the cell cycle compared with healthy cells. Many chemopreventive agents are thought to work by countering these alterations by inhibiting growth and proliferation, and ultimately induce apoptosis if necessary.
The Fight Against Cancer
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
Among the mechanisms in place to control the cell cycle are cascades involving a variety of proteins called cyclins, along with enzymes called cyclin-dependent kinases (CDK). Different types of each are responsible for the regulation of the different phases of the cell cycle. Binding of a cyclin with its enzyme activates the enzyme and serves to move the cell cycle from one phase to the next. Progression through the cell cycle is regulated by sequential activation of cyclins and CDKs. The process can also be down-regulated by CDK inhibiters.
Role of Plant-Based Bioflavonoids in Combating Tuberculosis
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Assessment of Medicinal Plants for Human Health, 2020
Alka Pawar, Yatendra Kumar Satija
Various reports have highlighted the role of flavonoids in chemoprevention. Cyclins and cyclin-dependent kinases (CDKs) are two types of regulatory molecules involved in the cell cycle progression. Activation of CDKs in an uncontrolled manner can lead to cancer. Therefore, to check this process, massive research has been focused on substances that can prevent or control CDKs activation. Many different flavonoids exhibited such activity, such as genistein, quercetin, daidzein, luteolin, kaempferol, apigenin, and epigallocatechin.24
Molecular pharmacology of multitarget cyclin-dependent kinase inhibitors in human colorectal carcinoma cells
Published in Expert Opinion on Therapeutic Targets, 2023
Sonal M. Manohar, Kalpana S. Joshi
The underlying biology of CRC is complex and heterogeneous making it one of the most interesting malignancies for exploring treatment options at this time [19]. There is an unmet medical need in order to treat patients with surgically incurable disease. We recently showed that multitarget CDK inhibitors serve as promising therapeutic drugs against CRC [20]. CDK inhibitors also exert off-target effects in cancer cells and their anticancer activity could be attributed to these effects as well [21–23]. Hence, preclinical studies to delineate these effects of such inhibitors are urgently needed in order to minimize toxicity and improve efficacy for CRC treatment. In this study we sought to determine, off-target effects of three CDK inhibitors with differing CDK inhibitory spectrum, on CRC cell lines viz. P276–00 (also known as riviciclib, earlier identified by our group) [24,25] (CDK1, 4, 9 specific), roscovitine (CDK2, 7, 9 specific) and UCN-01 (broad spectrum kinase inhibitor). We show that they differentially modulate signaling pathways in CRC. Their anticancer activity can be certainly attributed to these off-target effects.
Design, synthesis and molecular docking of new fused 1H-pyrroles, pyrrolo[3,2-d]pyrimidines and pyrrolo[3,2-e][1, 4]diazepine derivatives as potent EGFR/CDK2 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Amany Belal, Nagwa M. Abdel Gawad, Ahmed B. M. Mehany, Mohammed A. S. Abourehab, Hazem Elkady, Ahmed A. Al‐Karmalawy, Ahmed S. Ismael
The cyclin-dependent kinases (CDKs) are a group of enzymes involved in cell cycle progression and cellular proliferation24. They work by phosphorylating critical serine and threonine residues in host proteins, which then can activate them25,26. It is commonly believed that inhibiting CDKs could help the limitation of the uncontrolled cellular proliferation seen in some malignancies27. The majority of CDK inhibitors bind to the ATP pocket as ATP-competitive inhibitors with essential structural hydrogen-bonding motifs28. Cyclin-dependent kinase 2 (CDK2) belongs to the serine/threonine protein kinase family, and the CDK2 activity is found to be typically high in different types of human cancers. Studies have reported that CDK2 overexpression indicates poor prognosis in patients with HCC, and inhibition of CDK2 activity could reverse the malignant phenotype of cancer cells. Many studies revealed a key role of CDK2 in EGF-induced cell transformation and the associated signal transduction pathways29. The literature survey revealed that EGFR and CDK2 were the key targets for many antitumor agents e.g. cinobufagin30. In addition, biological and computational evidence supported that anticancer agents such as benzamide-substituted chalcones exerted their anti-proliferative effects via dual EGFR/CDK2 inhibitory activities31.
Pharmacophore-based virtual screening, synthesis, biological evaluation, and molecular docking study of novel pyrrolizines bearing urea/thiourea moieties with potential cytotoxicity and CDK inhibitory activities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Ahmed M. Shawky, Nashwa A. Ibrahim, Mohammed A. S. Abourehab, Ashraf N. Abdalla, Ahmed M. Gouda
Targeting the oncogenic protein kinases has emerged as a promising strategy in the development of new anticancer agents in the last three decades1,2. Currently, more than 40 kinase inhibitors were approved by the FDA for the treatment of different types of cancers3–5. Among these inhibitors, the cyclin-dependent kinase inhibitors (CDKIs) attracted much attention which could be due to the important role of CDKs in cell division and differentiation6,7. Among the CDK family, CDK-2 plays an important role in the progression of cells from G1 to S cell cycle phases6,7. The overexpression of CDK-2 was also reported in several solid tumours such as breast8, colon9, and ovarian cancers10. In addition, the increase in CDK-2 expression was also associated with the induction of the radio-resistance in glioblastoma cells11,12, and metastasis in prostate cancer13. CDK-2 also has a crucial role in DNA replication and apoptosis in different types of cancer6,12.