| Structural highlights
3rk9 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 3ql8, 3qqf, 3qqg, 3qqh, 3qqj, 3qqk, 3qql, 3qrt, 3qru, 3qtq, 3qtr, 3qts, 3qtu, 3qtw, 3qtx, 3qtz, 3qu0, 3qwj, 3qwk, 3qx2, 3qx4, 3qxo, 3qxp, 3qzf, 3qzg, 3qzh, 3qzi, 3r1q, 3r1s, 3r1y, 3r28, 3r6x, 3r71, 3r73, 3r7e, 3r7i, 3r7u, 3r7v, 3r7y, 3r83, 3r8l, 3r8m, 3r8p, 3r8u, 3r8v, 3r8z, 3r9d, 3r9h, 3r9n, 3r9o, 3rah, 3rai, 3rak, 3ral, 3rjc, 3rk5, 3rk7, 3rkb, 3rm6, 3rm7, 3rmf, 3rni, 3roy, 3rpo, 3rpr, 3rpv, 3rpy, 3rzb, 3s00, 3s0o, 3s1h, 3sqq |
| Gene: | CDK2 (Homo sapiens) |
| Activity: | Cyclin-dependent kinase, with EC number 2.7.11.22 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 muM) from a single hit compound with weak inhibitory activity (IC50 = 15 muM), discovered by high-throughput screening. Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound. The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 muM, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.
Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases.,Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI J Med Chem. 2013 May 6. PMID:23600925[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schonbrunn E, Betzi S, Alam R, Martin MP, Becker A, Han H, Francis R, Chakrasali R, Jakkaraj S, Kazi A, Sebti SM, Cubitt CL, Gebhard AW, Hazlehurst LA, Tash JS, Georg GI. Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases. J Med Chem. 2013 May 6. PMID:23600925 doi:10.1021/jm301234k
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