Warning: Undefined array key "mm" in /www/wwwroot/www.ai-bt.com/si.php on line 10 Deprecated: trim(): Passing null to parameter #1 ($string) of type string is deprecated in /www/wwwroot/www.ai-bt.com/si.php on line 10 4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6.

Literature DB >> 21038853

4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6.

Young Shin Cho¹, Maria Borland, Christopher Brain, Christine H-T Chen, Hong Cheng, Rajiv Chopra, Kristy Chung, James Groarke, Guo He, Ying Hou, Sunkyu Kim, Steven Kovats, Yipin Lu, Marc O'Reilly, Junqing Shen, Troy Smith, Gary Trakshel, Markus Vögtle, Mei Xu, Ming Xu, Moo Je Sung.

Abstract

Identification and structure-guided optimization of a series of 4-(pyrazol-4-yl)-pyrimidines as selective CDK4/6 inhibitors is reported herein. Several potency and selectivity determinants were established based on the X-ray crystallographic analysis of representative compounds bound to monomeric CDK6. Significant selectivity for CDK4/6 over CDK1 and CDK2 was demonstrated with several compounds in both enzymatic and cellular assays.

Entities: Chemical Gene

Mesh：

Substances：

Year: 2010 PMID： 21038853 DOI： 10.1021/jm100571n

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

Keyword Cloud
Cited

15 in total

Review 1. Targeting CDK6 in cancer: State of the art and new insights.

Authors: Solomon Tadesse; Mingfeng Yu; Malika Kumarasiri; Bich Thuy Le; Shudong Wang
Journal: Cell Cycle Date: 2015 Impact factor: 4.534

2. A strategy based on protein-protein interface motifs may help in identifying drug off-targets.

Authors: H Billur Engin; Ozlem Keskin; Ruth Nussinov; Attila Gursoy
Journal: J Chem Inf Model Date: 2012-07-31 Impact factor: 4.956

3. Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors.

Authors: Young Shin Cho; Hayley Angove; Christopher Brain; Christine Hiu-Tung Chen; Hong Cheng; Robert Cheng; Rajiv Chopra; Kristy Chung; Miles Congreve; Claudio Dagostin; Deborah J Davis; Ruth Feltell; John Giraldes; Steven D Hiscock; Sunkyu Kim; Steven Kovats; Bharat Lagu; Kim Lewry; Alice Loo; Yipin Lu; Michael Luzzio; Wiesia Maniara; Rachel McMenamin; Paul N Mortenson; Rajdeep Benning; Marc O'Reilly; David C Rees; Junqing Shen; Troy Smith; Yaping Wang; Glyn Williams; Alison J-A Woolford; Wojciech Wrona; Mei Xu; Fan Yang; Steven Howard
Journal: ACS Med Chem Lett Date: 2012-05-17 Impact factor: 4.345

4. Facile syntheses of novel benzo-1,3-dioxolo-, benzothiazolo-, pyrido-, and quinolino-fused 5H-benzo[d]-pyrazolo[5,1-b][1,3]-oxazines and 1H-pyrazoles.

Authors: Belem Avila; Danielle M Solano; Makhluf J Haddadin; Mark J Kurth
Journal: Org Lett Date: 2011-02-04 Impact factor: 6.005

4-(Pyrazol-4-yl)-pyrimidines as selective inhibitors of cyclin-dependent kinase 4/6.

Review 1. Targeting CDK6 in cancer: State of the art and new insights.

2. A strategy based on protein-protein interface motifs may help in identifying drug off-targets.

3. Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors.

4. Facile syntheses of novel benzo-1,3-dioxolo-, benzothiazolo-, pyrido-, and quinolino-fused 5H-benzo[d]-pyrazolo[5,1-b][1,3]-oxazines and 1H-pyrazoles.

5. Methods for Discovering and Targeting Druggable Protein-Protein Interfaces and Their Application to Repurposing.

Review 6. Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.

Review 7. Structure-based discovery of cyclin-dependent protein kinase inhibitors.

8. Discovery of new small-molecule cyclin-dependent kinase 6 inhibitors through computational approaches.

9. (2R)-4-[(9H-Fluoren-9-ylmeth-oxy)carbon-yl]-2-methyl-piperazin-1-ium chloride.

10. Drug targets for cell cycle dysregulators in leukemogenesis: in silico docking studies.