Structure-guided optimisation of <i>N</i>-hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-α-Reference-Cited by-同舟云学术

Structure-guided optimisation of N-hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-α

Published:2023 Issue:43 Volume:14 Page:12098-12120
ISSN:2041-6520
Container-title:Chemical Science
language:en
Short-container-title:Chem. Sci.

Author:

Corner Thomas P.¹^ORCID,Teo Ryan Z. R.¹^ORCID,Wu Yue²,Salah Eidarus¹,Nakashima Yu³^ORCID,Fiorini Giorgia¹,Tumber Anthony¹,Brasnett Amelia¹,Holt-Martyn James P.¹,Figg William D.¹,Zhang Xiaojin²^ORCID,Brewitz Lennart¹^ORCID,Schofield Christopher J.¹^ORCID

Affiliation:

1. Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, 12 Mansfield Road, OX1 3TA, Oxford, United Kingdom

2. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization and Department of Chemistry, China Pharmaceutical University, Nanjing 211198, China

3. Institute of Natural Medicine, University of Toyama, 2630-Sugitani, 930-0194, Toyama, Japan

Abstract

Optimised N-hydroxythiazoles are efficient and selective inhibitors of the 2-oxoglutrate dependent oxygenase factor inhibiting HIF, which has a key role in the human hypoxic response; the inhibitors decrease lipid accumualtion in adipocytes.

Funder

Wellcome Trust

Cancer Research UK

Biotechnology and Biological Sciences Research Council

GlaxoSmithKline

National Natural Science Foundation of China

Science Fund for Distinguished Young Scholars of Jiangsu Province

Diamond Light Source

University of Oxford

Royal Commission for the Exhibition of 1851

Publisher

Royal Society of Chemistry (RSC)