نتایج جستجو برای: at7519

تعداد نتایج: 29  

The strong storyline behind the critical role of cyclin-dependent kinase (CDK) inhibitor proteinsin natural defense against malignant transformation not only represents a heroic perspective forthese proteins, but also provides a bright future for the application of small molecule inhibitorsof CDKs in the novel cancer treatment strategies. The results of the present study revea...

Journal: :AIDS 2014
Eduardo Pauls Roger Badia Javier Torres-Torronteras Alba Ruiz Marc Permanyer Eva Riveira-Muñoz Bonaventura Clotet Ramón Marti Ester Ballana José A Esté

BACKGROUND Sterile α motif and HD domain-containing protein-1 (SAMHD1) inhibits HIV-1 reverse transcription by decreasing the pool of intracellular deoxynucleotides. SAMHD1 is controlled by cyclin-dependent kinase (CDK)-mediated phosphorylation. However, the exact mechanism of SAMHD1 regulation in primary cells is unclear. We explore the effect of palbociclib, a CDK6 inhibitor, in HIV-1 replica...

2014
Matthew G Guenther Jun Qi Zi Peng Fan Jason J Marineau Peter B Rahl Jakob Loven Lars Anders Matthew G. Guenther Jason J. Marineau Peter B. Rahl Jakob Lovén Alla A. Sigova William B. Smith Tong Ihn Lee James E. Bradner Richard A. Young

A vast number of small-molecule ligands, including therapeutic drugs under development and in clinical use, elicit their effects by binding specific proteins associated with the genome. An ability to map the direct interactions of a chemical entity with chromatin genome-wide could provide new and important insights into chemical perturbation of cellular function. Here we describe a method that ...

Journal: :Journal of medicinal chemistry 2008
Paul G Wyatt Andrew J Woodhead Valerio Berdini John A Boulstridge Maria G Carr David M Cross Deborah J Davis Lindsay A Devine Theresa R Early Ruth E Feltell E Jonathan Lewis Rachel L McMenamin Eva F Navarro Michael A O'Brien Marc O'Reilly Matthias Reule Gordon Saxty Lisa C A Seavers Donna-Michelle Smith Matt S Squires Gary Trewartha Margaret T Walker Alison J-A Woolford

The application of fragment-based screening techniques to cyclin dependent kinase 2 (CDK2) identified multiple (>30) efficient, synthetically tractable small molecule hits for further optimization. Structure-based design approaches led to the identification of multiple lead series, which retained the key interactions of the initial binding fragments and additionally explored other areas of the ...

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