Title: General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors.
Authors: Vasilevich, Natalya I.; Aksenova, Elena A.; Kazyulkin, Denis N.; Afanasyev, Ilya I.
Abstract: A general pharmachophore model for various types of Ser/ Thr kinases was developed. Search for the molecules fitting to this pharmacophore among ASINEX proprietary library revealed a number of compounds, which were tested and appeared to possess some activity against several Ser/ Thr kinases such as Aurora A, Aurora B and Haspin. The possibility of performing the fine-tuning of the general Ser/ Thr pharmacophore to desired types of kinase to get active and selective inhibitors was exemplified by Aurora A kinase. As a result, several hits in 3-5 n m range of activity against Aurora A kinase with rather good selectivity and ADME properties were obtained.
Subjects: SERINE/THREONINE kinases; KINASE inhibitors; AURORA kinases; DRUG design; THIAZOLE derivatives; PYRAZOLES; HETEROCYCLIC compounds synthesis
Publication: Chemical Biology & Drug Design, 2016, Vol 88, Issue 1, p54
ISSN: 1747-0277
Publication type: Academic Journal
DOI: 10.1111/cbdd.12733

General Ser/Thr Kinases Pharmacophore Approach for Selective Kinase Inhibitors Search as Exemplified by Design of Potent and Selective Aurora A Inhibitors.

Vasilevich, Natalya I.; Aksenova, Elena A.; Kazyulkin, Denis N.; Afanasyev, Ilya I.