Evidence map›Paper›PMID 38505861›Full record

ArticleACS medicinal chemistry letters2024

Discovery of Alternative Binding Poses through Fragment-Based Identification of DHODH Inhibitors.

Lindsey G DeRatt, E Christine Pietsch, Justin S Cisar, Edgar Jacoby, Faraz Kazmi, Rosalie Matico, Paul Shaffer, Alexandra Tanner, Weixue Wang, Ricardo Attar and 2 more

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2024. 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
–field-weighted citation impact
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.

  1. Article
  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

12 authors.

Lindsey G DeRattJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.ORCID https://orcid.org/0000-0002-0412-8111
E Christine PietschJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Justin S CisarJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.ORCID https://orcid.org/0000-0002-8693-9670
Edgar JacobyJanssen Pharmaceutical Research and Development, Turnhoutseweg 30, 2340 Beerse, Belgium.
Faraz KazmiJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Rosalie MaticoJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Paul ShafferJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Alexandra TannerJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Weixue WangJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Ricardo AttarJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
James P EdwardsJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.
Scott D KudukJanssen Pharmaceutical Research and Development, 1400 McKean Rd., Spring House, Pennsylvania 19477, United States.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that affects many aspects essential to cell proliferation and survival. Recently, DHODH has been identified as a potential target for acute myeloid leukemia therapy. Herein, we describe the identification of potent DHODH inhibitors through a scaffold hopping approach emanating from a fragment screen followed by structure-based drug design to further improve the overall profile and reveal an unexpected novel binding mode. Additionally, these compounds had low P-gp efflux ratios, allowing for applications where exposure to the brain would be required.

Identifiers

PMID38505861
PMCPMC10945543

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.