ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

Willmen Youngsaye; Cathy L. Hartland; Barbara J. Morgan; Amal Ting; Partha P. Nag; Benjamin Vincent; Carrie A. Mosher; Joshua A. Bittker; Sivaraman Dandapani; Michelle Palmer; Luke Whitesell; Susan Lindquist; Stuart L. Schreiber; Benito Munoz

doi:10.3762/bjoc.9.171

Beilstein Journal of Organic Chemistry (Jul 2013)

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

Willmen Youngsaye,
Cathy L. Hartland,
Barbara J. Morgan,
Amal Ting,
Partha P. Nag,
Benjamin Vincent,
Carrie A. Mosher,
Joshua A. Bittker,
Sivaraman Dandapani,
Michelle Palmer,
Luke Whitesell,
Susan Lindquist,
Stuart L. Schreiber,
Benito Munoz

Affiliations

Willmen Youngsaye: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Cathy L. Hartland: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Barbara J. Morgan: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Amal Ting: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Partha P. Nag: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Benjamin Vincent: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Carrie A. Mosher: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Joshua A. Bittker: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Sivaraman Dandapani: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Michelle Palmer: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Luke Whitesell: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Susan Lindquist: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA
Stuart L. Schreiber: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA
Benito Munoz: Chemical Biology Platform and Probe Development Center, Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA

DOI: https://doi.org/10.3762/bjoc.9.171
Journal volume & issue: Vol. 9, no. 1
pp. 1501 – 1507

Abstract

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The National Institutes of Health Molecular Libraries and Probe Production Centers Network (NIH-MLPCN) screened >300,000 compounds to evaluate their ability to restore fluconazole susceptibility in resistant Candida albicans isolates. Additional counter screens were incorporated to remove substances inherently toxic to either mammalian or fungal cells. A substituted indazole possessing the desired bioactivity profile was selected for further development, and initial investigation of structure–activity relationships led to the discovery of ML212.

Published in Beilstein Journal of Organic Chemistry

ISSN: 1860-5397 (Online)
Publisher: Beilstein-Institut
Country of publisher: Germany
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.beilstein-journals.org/bjoc

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Abstract

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