Efficient Optimization Strategy for Marginal Hits Active Against abl Tyrosine Kinases

Title: Efficient Optimization Strategy for Marginal Hits Active Against abl Tyrosine Kinases

Volume: 1 Issue: 3

Author(s): Sergey E. Tkachenko, Ilya Okun, Konstantin V. Balakin, Charles E. Petersen, Yan A. Ivanenkov, Nikolay P. Savchuk and Andrey A. Ivashchenko

Affiliation:

Keywords: high-throughput screening, combinatorial synthesis, virtual screening, tyrosine kinase inhibitors, hit optimization, bioisosteric approach, quantitative structure-activity relationship, support vector machines

Abstract: Primary high-throughput screening of commercially available small molecules collections often results in hit compounds with unfavorable ADME / Tox properties and low IP potential. These issues are addressed empirically at follow-up lead development and optimization stages. In this work, we describe a rational approach to the optimization of hit compounds discovered during screening of a kinase focused library against abl tyrosine kinase. The optimization strategy involved application of modern chemoinformatics techniques, such as automatic bioisosteric transformation of the initial hits, efficient solution-phase combinatorial synthesis, and advanced methods of knowledge-based libraries design.

Cite this article as:

Tkachenko E. Sergey, Okun Ilya, Balakin V. Konstantin, Petersen E. Charles, Ivanenkov A. Yan, Savchuk P. Nikolay and Ivashchenko A. Andrey, Efficient Optimization Strategy for Marginal Hits Active Against abl Tyrosine Kinases, Current Drug Discovery Technologies 2004; 1 (3) . https://dx.doi.org/10.2174/1570163043335018