ArticleChemMedChem2020
Elucidation of an Allosteric Mode of Action for a Thienopyrazole RORγt Inverse Agonist.
Article in ChemMedChem, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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.
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.
Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Circadian rhythms in the tumor microenvironment: spatiotemporal immune regulation and chronotherapeutic opportunities.Frontiers in immunology · 2026Review
- Statistical Analysis of Protein-Ligand Interaction Patterns in Nuclear Receptor RORγ.Frontiers in molecular biosciences · 2022Article
- Structure-Activity Relationship Studies of Trisubstituted Isoxazoles as Selective Allosteric Ligands for the Retinoic-Acid-Receptor-Related Orphan Receptor γt.Journal of medicinal chemistry · 2021Article
- Covalent Occlusion of the RORγt Ligand Binding Pocket Allows Unambiguous Targeting of an Allosteric Site.ACS medicinal chemistry letters · 2021Article
- Orthosteric and Allosteric Dual Targeting of the Nuclear Receptor RORγt with a Bitopic Ligand.ACS chemical biology · 2021Article
- Cooperativity between the orthosteric and allosteric ligand binding sites of RORγt.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- RORγ Structural Plasticity and Druggability.International journal of molecular sciences · 2020Review
- Delineation of the molecular determinants of the unique allosteric binding site of the orphan nuclear receptor RORγt.The Journal of biological chemistry · 2020Article
- Elucidation of an Allosteric Mode of Action for a Thienopyrazole RORγt Inverse Agonist.ChemMedChem · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The demand for allosteric targeting of nuclear receptors is high, but examples are limited, and structural information is scarce. The retinoic acid-related orphan receptor gamma t (RORγt) is an important transcriptional regulator for the differentiation of T helper 17 cells for which the first, and some of the most promising, examples of allosteric nuclear receptor modulation have been reported and structurally proven. In a 2015 patent, filed by the pharmaceutical company Glenmark, a new class of small molecules was reported that act as potent inverse agonists for RORγt. A compound library around the central thienopyrazole scaffold captured a clear structure-activity relationship, but the binding mechanism of this new class of RORγt modulators has not been elucidated. Using a combination of biochemical and X-ray crystallography studies, here the allosteric mechanism for the inverse agonism for the most potent compound, classified in the patent as "example 13", is reported, providing a strongly desired additional example of allosteric nuclear receptor targeting.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.