An Integrated Drug Development Approach Applying Topological Descriptors

Title:An Integrated Drug Development Approach Applying Topological Descriptors

Volume: 8 Issue: 3

Author(s): Alan Talevi, Carolina L. Bellera, Mauricio Di Ianni, Pablo R. Duchowicz, Luis E. Bruno-Blanch and Eduardo A. Castro

Affiliation:

Keywords: ADMET filters, classifiers, drug repurposing, linear models, QSAR, replacement method, topological descriptors, virtual screening, CNS disorders, high-throughput screening

Abstract: We describe the opportunities posed by computer-assisted drug design in the light of two aspects of the current drug discovery scenario: the decline of innovation due to high attrition rates at clinical stage of development and the combinatorial explosion emerging from exponential growth of feasible small molecules and genome and proteome exploration.

We present an overview of recent reports from our group in the field of rational drug development, by using topological descriptors (either alone, or in combination with different 3D approaches) and a diversity of modeling techniques such as Linear Discriminant Analysis and the Replacement Method. Modeling efforts aimed at the integrated prediction of several significant molecular properties in the field of drug discovery, such as pharmacological activity, aqueous solubility, human intestinal permeability and affinity to P-glycoprotein (ABCB1, MDR1) are reviewed. The suitability of conformation-independent descriptors to explore large chemical repositories is highlighted, as well as the opportunities posed by in silico guided drug repurposing.

Cite this article as:

Talevi Alan, L. Bellera Carolina, Di Ianni Mauricio, R. Duchowicz Pablo, E. Bruno-Blanch Luis and A. Castro Eduardo, An Integrated Drug Development Approach Applying Topological Descriptors, Current Computer-Aided Drug Design 2012; 8 (3) . https://dx.doi.org/10.2174/157340912801619076