Ligand efficiency indices for effective drug discovery.

Ligand efficiency indices for an effective mapping of chemico-biological space: the concept of an atlas-like representation.

We propose a numerical framework that permits an effective atlas-like representation of chemico-biological space based on a series of Cartesian planes mapping the ligands with the corresponding targets connected by an affinity parameter (K(i) or related). The numerical framework is derived from the concept of ligand efficiency indices, which provide a natural coordinate system combining the pot...

Ligand efficiency indices as guideposts for drug discovery.

In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent Discovery

Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of non compliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need...

Two 'Golden Ratio' indices in fragment-based drug discovery.

Fragment-based drug discovery (FBDD) is complementary to high-throughput screening. The approach has two key stages: identifying the starting fragment hit to be developed and generating the lead compound from the starting fragment hit. Here, we provide an overview of FBDD and introduce two indices originally developed at Astellas Pharma. The first is related to the size ratio of fragment hits t...

Fragment-based Binding Efficiency Indices in Bioactive Molecular Design: A Computational Approach to BACE-1 Inhibitors

One of the most important targets in Alzheimer disease is Beta site amyloid precursor protein cleaving enzyme-1 (BACE-1). It is a membrane associated protein and is one of the main enzymes responsible for amyloid β (Aβ) production. Up to now, a considerable number of peptidic and non-peptidic inhibitors of BACE-1 have been developed. Recently, small molecule BACE-1 inhibitors have attracted the...