ArticleACS medicinal chemistry letters2018
Discovery of a First-in-Class Gut-Restricted RET Kinase Inhibitor as a Clinical Candidate for the Treatment of IBS.
Article in ACS medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Meta-analysis of gut microbiota alterations in patients with irritable bowel syndrome.Frontiers in microbiology · 2024Pooled it
- Unique fluoroalkyl substituents: is there life after CFChemical science · 2026Review
- Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- GSK3179106 ameliorates lipopolysaccharide-induced inflammation and acute lung injury by targeting P38 MAPK.Respiratory research · 2024Article
- RET Signaling Persists in the Adult Intestine and Stimulates Motility by Limiting PYY Release From Enteroendocrine Cells.Gastroenterology · 2024Article
- Design and Synthesis of Novel Thieno[3,2-ACS omega · 2023Article
- A branching model of lineage differentiation underpinning the neurogenic potential of enteric glia.Nature communications · 2023Article
- Trust Your Gut: Strategies and Tactics for Intestinally Restricted Drugs.ACS medicinal chemistry letters · 2023Review
- Improving the performance of single-cell RNA-seq data mining based on relative expression orderings.Briefings in bioinformatics · 2023Article
- Recent Advances in Pain Management: Relevant Protein Kinases and Their Inhibitors.Molecules (Basel, Switzerland) · 2021Review
- Acute stress disrupts intestinal homeostasis via GDNF-RET.Cell proliferation · 2020Article
- Efficacy and Tolerability of Pyrazolo[1,5-ACS medicinal chemistry letters · 2020Article
- Measurement of novel intestinal secretory and barrier pathways and effects of proteases.Neurogastroenterology and motility · 2019Review
- Exploring the Potential of RET Kinase Inhibition for Irritable Bowel Syndrome: A Preclinical Investigation in Rodent Models of Colonic Hypersensitivity.The Journal of pharmacology and experimental therapeutics · 2019Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abdominal pain and abnormal bowel habits represent major symptoms for irritable bowel syndrome (IBS) patients that are not adequately managed. Although the etiology of IBS is not completely understood, many of the functions of the gastrointestinal (GI) tract are regulated by the enteric nervous system (ENS). Inflammation or stress-induced expression of growth factors or cytokines may lead to hyperinnervation of visceral afferent neurons in GI tract and contribute to the pathophysiology of IBS. Rearranged during transfection (RET) is a neuronal growth factor receptor tyrosine kinase critical for the development of the ENS as exemplified by Hirschsprung patients who carry RET loss-of-function mutations and lack normal colonic innervation leading to colonic obstruction. Similarly, RET signaling in the adult ENS maintains neuronal function by contributing to synaptic formation, signal transmission, and neuronal plasticity. Inhibition of RET in the ENS represents a novel therapeutic strategy for the normalization of neuronal function and the symptoms of IBS patients. Herein, we describe our screening effort and subsequent structure-activity relationships (SARs) in optimizing potency, selectivity, and mutagenicity of the series, which led to the discovery of a first-in-class, gut-restricted RET kinase inhibitor, 2-(4-(4-ethoxy-6-oxo-1,6-dihydropyridin-3-yl)-2-fluorophenyl)-
Identifiers
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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.