Evidence map›Paper›PMID 35586440›Full record

ArticleACS medicinal chemistry letters2022

Identification of 2-Pyridinylindole-Based Dual Antagonists of Toll-like Receptors 7 and 8 (TLR7/8).

Ratna Kumar Sreekantha, Christopher P Mussari, Dharmpal S Dodd, Laxman Pasunoori, Subramanya Hegde, Shana L Posy, David Critton, Stefan Ruepp, Murali Subramanian, Luisa M Salter-Cid and 8 more

Abstract read
In one paragraph

Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

18 authors.

Ratna Kumar SreekanthaBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Christopher P MussariBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Dharmpal S DoddBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Laxman PasunooriBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Subramanya HegdeBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Shana L PosyBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
David CrittonBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Stefan RueppBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Murali SubramanianBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Luisa M Salter-CidBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Debarati Mazumder TagoreBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Sanket SarodayaBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Shailesh DudhgaonkarBiocon Bristol Myers Squibb Research Center (BBRC), Bangalore 560099, India.
Michael A PossBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.ORCID https://orcid.org/0000-0002-2423-8553
Gary L SchievenBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Percy H CarterBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
John E MacorBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.
Alaric J DyckmanBristol Myers Squibb Research and Development, P.O. Box 4000, Princeton, New Jersey 08543, United States.ORCID https://orcid.org/0000-0002-1050-2077

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The toll-like receptors (TLRs) play key roles in activation of the innate immune system. Aberrant activation of TLR7 and TLR8 pathways can occur in the context of autoimmune disorders due to the elevated presence and recognition of self-RNA as activating ligands. Control of this unintended activation via inhibition of TLR7/8 signaling holds promise for the treatment of diseases such as psoriasis, arthritis, and lupus. Optimization of a 2-pyridinylindole series of compounds led to the identification of potent dual inhibitors of TLR7 and TLR8, which demonstrated good selectivity against TLR9 and other family members. The in vitro characterization and in vivo evaluation in rodent pharmacokinetic/pharmacodynamic and efficacy studies of BMS-905 is detailed, along with structural information obtained through X-ray cocrystallographic studies.

Identifiers

PMID35586440
PMCPMC9109266

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.