Abelson Tyrosine-Protein Kinase 1 as Principal Target for Drug Discovery Against Leukemias. Role of the Current Computer-Aided Drug Design Methodologies

• Type: Another Publication in an International Scientific Journal
• Date: 2012

Authors

Alejandro Speck Planche (Author) Other; Feng Luan (Author) Other; Cordeiro, MNDS (Author) FCUP

Journal

Title: Current Topics in Medicinal Chemistry

Vol. 12

Pages: 2745-2762

ISSN: 1568-0266

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 19 Citations

Scopus - 18 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-005-3SK

Abstract (EN): The discovery of anti-cancer agents is an area which continues in accelerated expansion. Leukemias (Lkms) are among the most investigated cancers due to its high and dominant prevalence in children. Computer-aided drug design (CADD) methodologies have been extremely important for the discovery of potent anti-Lkms agents, providing essential insights about the molecular patterns which could be involved in the appearance and development of anti-Lkms activity. The present review is focused on the role of the current CADD methodologies for the discovery of anti-Lkms agents with strong emphasis on the in silico prediction of inhibitors against the primary protein associated with the appearance of Lkms: Abelson tyrosine-protein kinase 1 (TPK-ABL1). In order to make a contribution to the field, we also developed a unified ligand-based approach by exploring Quantitative-Structure Activity Relationships (QSAR) studies. Here, we focused on the construction of two multi-targets (mt) QSAR models by employing a large and heterogeneous database of compounds. These models exhibited excellent statistical quality and predictive power to classifying more than 92% of inhibitors/no inhibitors against seven proteins associated with Lkms, in both training and prediction sets. By using our unified ligand-based approach we identified several fragments as responsible for the anti-Lkms activity through inhibition of proteins, and new molecules were suggested as versatile inhibitors of the seven proteins under study.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 18