Evidence map›Paper›PMID 34531952›Full record

ArticleACS medicinal chemistry letters2021

Utilization of Metabolite Identification and Structural Data to Guide Design of Low-Dose IDO1 Inhibitors.

Brett Hopkins, Hongjun Zhang, Indu Bharathan, Derun Li, Qinglin Pu, Hua Zhou, Theodore A Martinot, Xavier Fradera, Alfred Lammens, Charles A Lesburg and 13 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.5field-weighted citation impact, top 47% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 1 institution in 1 country.

Brett HopkinsDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Hongjun ZhangDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0002-1136-6142
Indu BharathanDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Derun LiDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0003-0512-6684
Qinglin PuDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0002-7853-4542
Hua ZhouDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Theodore A MartinotDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0003-2290-9621
Xavier FraderaDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0002-6118-075X
Alfred LammensProteros Biostructures GmbH, Bunsenstraße 7a, D-82152 Planegg-Martinsried, Germany.
Charles A LesburgDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0001-7245-7331
Ryan D CohenAnalytical Research and Development, Merck & Co., Inc., Rahway, New Jersey 07065, United States.ORCID https://orcid.org/0000-0002-3112-6410
Jeanine BallardDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Ian KnemeyerDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Karin OtteDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Stella VincentDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
J Richard MillerDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Nicolas SolbanDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Mangeng ChengDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Prasanthi GedaDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Nadya SmotrovDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Xuelei SongDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
David Jonathan BennettDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
Yongxin HanDepartments of Discovery Chemistry, Pharmacokinetics, Pharmacodynamics, and Drug Metabolism, Computational and Structural Chemistry, Discovery Process Chemistry, and Pharmacology, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.ORCID https://orcid.org/0000-0002-3014-035X
Merck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Herein the discovery of potent IDO1 inhibitors with low predicted human dose is discussed. Metabolite identification (MetID) and structural data were used to strategically incorporate cyclopropane rings into this tetrahydronaphthyridine series of IDO1 inhibitors to improve their metabolic stability and potency. Enabling synthetic chemistry was developed to construct these unique fused cyclopropyl compounds, leading to inhibitors with improved pharmacokinetics and human whole blood potency and a predicted human oral dose as low as 9 mg once daily (QD).

Identifiers

PMID34531952
PMCPMC8436249
OpenAlexW3194853892

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.