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Literature DB >> 18993068

Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.

David J Kopecky¹, Xiaolin Hao, Yi Chen, Jiasheng Fu, XianYun Jiao, Juan C Jaen, Mario G Cardozo, Jinsong Liu, Zhulun Wang, Nigel P C Walker, Holger Wesche, Shyun Li, Ellyn Farrelly, Shou-Hua Xiao, Frank Kayser.

Abstract

A new series of pyrazolo[3,4-d]pyrimidine-3,6-diamines was designed and synthesized as potent and selective inhibitors of the nonreceptor tyrosine kinase, ACK1. These compounds arose from efforts to rigidify an earlier series of N-aryl pyrimidine-5-carboxamides. The synthesis and structure-activity relationships of this new series of inhibitors are reported. The most promising compounds were also profiled for their pharmacokinetic properties.

Entities: Chemical Gene

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Year: 2008 PMID： 18993068 DOI： 10.1016/j.bmcl.2008.10.092

Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823

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Cited

10 in total

1. Methyl effects on protein-ligand binding.

Authors: Cheryl S Leung; Siegfried S F Leung; Julian Tirado-Rives; William L Jorgensen
Journal: J Med Chem Date: 2012-04-23 Impact factor: 7.446

2. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors.

Authors: Chandrasekhar V Miduturu; Xianming Deng; Nicholas Kwiatkowski; Wannian Yang; Laurent Brault; Panagis Filippakopoulos; Eunah Chung; Qingkai Yang; Juerg Schwaller; Stefan Knapp; Randall W King; Jiing-Dwan Lee; Sanna Herrgard; Patrick Zarrinkar; Nathanael S Gray
Journal: Chem Biol Date: 2011-07-29

3. Development of novel ACK1/TNK2 inhibitors using a fragment-based approach.

Authors: Harshani R Lawrence; Kiran Mahajan; Yunting Luo; Daniel Zhang; Nathan Tindall; Miles Huseyin; Harsukh Gevariya; Sakib Kazi; Sevil Ozcan; Nupam P Mahajan; Nicholas J Lawrence
Journal: J Med Chem Date: 2015-03-17 Impact factor: 7.446

4. Estimation of relative free energies of binding using pre-computed ensembles based on the single-step free energy perturbation and the site-identification by Ligand competitive saturation approaches.

Authors: E Prabhu Raman; Sirish Kaushik Lakkaraju; Rajiah Aldrin Denny; Alexander D MacKerell
Journal: J Comput Chem Date: 2016-10-26 Impact factor: 3.376

Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.

1. Methyl effects on protein-ligand binding.

2. High-throughput kinase profiling: a more efficient approach toward the discovery of new kinase inhibitors.

3. Development of novel ACK1/TNK2 inhibitors using a fragment-based approach.

4. Estimation of relative free energies of binding using pre-computed ensembles based on the single-step free energy perturbation and the site-identification by Ligand competitive saturation approaches.

5. Efficient Hit-to-Lead Searching of Kinase Inhibitor Chemical Space via Computational Fragment Merging.

6. A novel multi-modal drug repurposing approach for identification of potent ACK1 inhibitors.

Review 7. ACK1 tyrosine kinase: targeted inhibition to block cancer cell proliferation.

8. Effect of set up protocols on the accuracy of alchemical free energy calculation over a set of ACK1 inhibitors.

9. ACK1-AR and AR-HOXB13 signaling axes: epigenetic regulation of lethal prostate cancers.

10. Ack1: activation and regulation by allostery.