Figure 2 from Novel Inhibitors of Cyclin Biology Diagrams Cell cycle inhibitors prevent unchecked proliferation by inhibiting CDKs. These inhibitors fall into two families: INK4 (p15, p16, p18, p19) and Cip/Kip (p21, p27, p57). INK4 proteins inhibit CDK4 and CDK6, blocking cyclin D interaction and preventing G1 progression. Cip/Kip proteins have broader specificity, inhibiting multiple CDKs and CDK inhibitors have been studied since the 1990s. The first generation of CDK inhibitors are pan-CDK inhibitors, including Flavopiridol and Roscovitine, etc. The main function of these inhibitors is to block cell cycle and inhibit cell proliferation by inhibiting the CDK enzyme activity. Major cell cycle regulatory proteins inhibitors (CDK inhibitors) under clinical evaluation. Cyclin-dependent kinases (CDKs) and the regulatory components of these enzymes, called cyclins, regulate the cell cycle by temporally controlling kinase activity and substrate selectivity. (A) CDK-cyclin complexes, comprising 10 cyclins from 4 different
First identified as cell cycle inhibitors mediating the growth inhibitory cues of upstream signaling pathways, the cyclin-CDK inhibitors of the Cip/Kip family p21Cip1, p27Kip1, and p57Kip2 have emerged as multifaceted proteins with functions beyond cell cycle regulation. In addition to regulating the cell cycle, Cip/Kip proteins play important roles in apoptosis, transcriptional regulation Example of inhibitors that, in early clinical trials, are targeting cyclin-dependent kinases (cdk s) acting in or outside of the cell cycle.Inhibitors of cdk also inhibit transcription. A key enzyme in the transcription machinery, rna polymerase ii, is phosphorylated by several cdk s 34, 35.The most important regulator is cdk 9/cyclin T. Inhibition of cdk 9/cyclin T by a cdki such as Inhibits cell cycle at G 1 phase; also SMO antagonist: 7157: YKL 5-124: Potent and selective CDK7 inhibitor; induces cell cycle arrest at the G 1 /S transition: Other; Cat. No. Product Name / Activity; 4406: 10058-F4: Arrests cell cycle at G 0 /G 1: 7680: ABT 263: Induces G 1 /G 0 phase arrest; Bcl-2 family inhibitor: 3968:
Cell cycle regulation and anticancer drug discovery Biology Diagrams
Deregulation of the cell cycle is a hallmark of the transformation of normal cells into tumor cells. Given its importance in tumorigenesis, several cell cycle inhibitors have emerged as potential therapeutic drugs for the treatment of cancers-both as single-agent therapy and in combination with traditional cytotoxic or molecular targeting agents.
The cell cycle blockade imposed by CDK4/CDK6 inhibitors is not necessarily irreversible 64,66, and this may contribute to disease progression not only upon the recovery of tumour cell Keywords: cyclin-dependent kinase inhibitors, cancer, cell cycle, CDKs, CDK inhibitors. 1. Cyclin-Dependent Kinases (CDKs) Protein phosphorylation is a necessary mechanism to drive numerous cellular processes such as cell division, migration, differentiation and programmed cell death. This process is regulated by many enzymes, including cyclin
