Strategic Incorporation of Polarity in Heme-Displacing Inhibitors of Indoleamine-2,3-dioxygenase-1 (IDO1).


Journal

ACS medicinal chemistry letters
ISSN: 1948-5875
Titre abrégé: ACS Med Chem Lett
Pays: United States
ID NLM: 101521073

Informations de publication

Date de publication:
09 Apr 2020
Historique:
received: 06 01 2020
accepted: 10 03 2020
entrez: 16 4 2020
pubmed: 16 4 2020
medline: 16 4 2020
Statut: epublish

Résumé

Indoleamine-2,3-dioxygenase-1 (IDO1) has emerged as a target of significant interest to the field of cancer immunotherapy, as the upregulation of IDO1 in certain cancers has been linked to host immune evasion and poor prognosis for patients. In particular, IDO1 inhibition is of interest as a combination therapy with immune checkpoint inhibition. Through an Automated Ligand Identification System (ALIS) screen, a diamide class of compounds was identified as a promising lead for the inhibition of IDO1. While hit

Identifiants

pubmed: 32292563
doi: 10.1021/acsmedchemlett.0c00010
pmc: PMC7153270
doi:

Types de publication

Journal Article

Langues

eng

Pagination

550-557

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Catherine White (C)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Meredeth A McGowan (MA)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Hua Zhou (H)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Nunzio Sciammetta (N)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Xavier Fradera (X)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Jongwon Lim (J)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Elizabeth M Joshi (EM)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Christine Andrews (C)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Elliott B Nickbarg (EB)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Phillip Cowley (P)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Sarah Trewick (S)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Martin Augustin (M)

Proteros biostructures GmbH, 82152 Martinsried, Germany.

Konstanze von Köenig (K)

Proteros biostructures GmbH, 82152 Martinsried, Germany.

Charles A Lesburg (CA)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Karin Otte (K)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Ian Knemeyer (I)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Hyun Woo (H)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Wensheng Yu (W)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Mangeng Cheng (M)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Peter Spacciapoli (P)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Prasanthi Geda (P)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Xuelei Song (X)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Nadya Smotrov (N)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Patrick Curran (P)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Mee Ra Heo (MR)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Pravien Abeywickrema (P)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

J Richard Miller (JR)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

David Jonathan Bennett (DJ)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Yongxin Han (Y)

Department of Chemistry, Computational and Structural Chemistry, Pharmacokinetics, Pharmacodynamics & Drug Metabolism, Quantitative Biosciences, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.

Classifications MeSH