Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1–Nrf2 Protein–Protein Interaction-Reference-Cited by-同舟云学术

Importance of Binding Site Hydration and Flexibility Revealed When Optimizing a Macrocyclic Inhibitor of the Keap1–Nrf2 Protein–Protein Interaction

Published:2022-02-02 Issue:4 Volume:65 Page:3473-3517
ISSN:0022-2623
Container-title:Journal of Medicinal Chemistry
language:en
Short-container-title:J. Med. Chem.

Author:

Begnini Fabio¹,Geschwindner Stefan²^ORCID,Johansson Patrik²,Wissler Lisa²,Lewis Richard J.³^ORCID,Danelius Emma¹,Luttens Andreas⁴^ORCID,Matricon Pierre⁴^ORCID,Carlsson Jens⁴^ORCID,Lenders Stijn¹^ORCID,König Beate¹,Friedel Anna¹,Sjö Peter⁵,Schiesser Stefan³^ORCID,Kihlberg Jan¹^ORCID

Affiliation:

1. Department of Chemistry─BMC, Uppsala University, Box 576, 75123 Uppsala, Sweden

2. Mechanistic and Structural Biology, Discovery Sciences, R&D, AstraZeneca, 43183 Mölndal, Sweden

3. Department of Medicinal Chemistry, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca, 43183 Mölndal, Sweden

4. Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, Box 596, 75124 Uppsala, Sweden

5. Drugs for Neglected Diseases Initiative (DNDi), 15 Chemin Camille-Vidart, 1202 Geneva, Switzerland

Funder

AstraZeneca

Vetenskapsrådet

Publisher

American Chemical Society (ACS)

Subject

Drug Discovery,Molecular Medicine

Link

https://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.1c01975

Reference60 articles.