Cell-based medicinal chemistry optimization of high throughput screening hits for orally active antimalarials. Part 2: hits from SoftFocus kinase and other libraries

Yassir Younis; Leslie J Street; David Waterson; Michael J Witty; Kelly Chibale

doi:10.1021/jm400279y

Cell-based medicinal chemistry optimization of high throughput screening hits for orally active antimalarials. Part 2: hits from SoftFocus kinase and other libraries

J Med Chem. 2013 Oct 24;56(20):7750-4. doi: 10.1021/jm400279y. Epub 2013 Aug 30.

Authors

Yassir Younis¹, Leslie J Street, David Waterson, Michael J Witty, Kelly Chibale

Affiliation

¹ Department of Chemistry, University of Cape Town , Rondebosch 7701, South Africa.

PMID: 23927599
DOI: 10.1021/jm400279y

Abstract

In the second part of this Miniperspectives series, we highlight our medicinal chemistry efforts involving progression of hits from whole cell high-throughput screening (HTS) of a SoftFocus kinase library against the malaria parasite Plasmodium falciparum . Successful SAR exploration in Hit-to-Lead and Lead Optimization efforts leading to the selection of a preclinical development candidate are demonstrated. Related efforts by researchers from Broad/Genzyme, Anacor, and GSK are briefly covered.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Administration, Oral
Antimalarials / administration & dosage
Antimalarials / chemistry
Antimalarials / therapeutic use*
Chemistry, Pharmaceutical / methods*
Drug Discovery / methods*
Drug Evaluation, Preclinical
Humans
Malaria, Falciparum / parasitology
Malaria, Falciparum / prevention & control
Molecular Structure
Plasmodium falciparum / drug effects
Structure-Activity Relationship

Substances

Antimalarials