Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties

McKinnell, R. Murray; Armstrong, Scott R.; Beattie, David T.; Fatheree, Paul R.; Long, Daniel D.; Marquess, Daniel G.; Shaw, Jeng‐Pyng; Vickery, Ross G.

doi:10.1016/j.bmcl.2013.05.018

Cited by 14 publications

(13 citation statements)

References 26 publications

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“…Editorial: felcisetrag-forward movement as a novel prokinetic for gastroparesis 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonists promote intestinal peristalsis, increase gastric emptying and improve oesophageal motility. Accordingly, 5-HT 4 agonists hold strong potential to improve hypomotility symptoms via their prokinetic properties.…”

Section: N V I T E D E D I T O R I a Lmentioning

confidence: 99%

Editorial: felcisetrag—forward movement as a novel prokinetic for gastroparesis

Rogers

Sayuk

2021

Aliment Pharmacol Ther

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Section: N V I T E D E D I T O R I a Lmentioning

confidence: 99%

Editorial: felcisetrag—forward movement as a novel prokinetic for gastroparesis

Rogers

Sayuk

2021

Aliment Pharmacol Ther

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“…It is a selective 5-HT 4 receptor agonist with good intrinsic activity [43]. Subcutaneous administration of TD-8954 (0.03–3mg/kg) increased colonic transit of carmine red dye in guinea pigs, and it evoked a dose dependent (10 and 30μg/kg) relaxation of the esophagus in rats.…”

Section: Early Investigational Therapeuticsmentioning

confidence: 99%

Early investigational therapeutics for gastrointestinal motility disorders: from animal studies to Phase II trials

Valentin

Acosta

Camilleri

2015

Expert Opinion on Investigational Drugs

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Introduction The most common gastrointestinal disorders which include evidence of dysmotility include: gastroparesis, the lower functional gastrointestinal disorders associated with altered bowel function [such as chronic (functional) diarrhea, chronic idiopathic constipation (CIC)], and opioid induced constipation (OIC). These conditions, which are grouped as gastrointestinal motility and functional disorders, are characterized by abnormal motor, sensory, or secretory functions that alter bowel function and result in a significant disease burden, since currently available treatments do not completely alleviate symptoms. New drugs are being developed for these disorders, targeting mechanisms involved in the pathophysiology of these diseases, specifically, motor function, intestinal secretion and bile acid modulation. Areas Covered The article provides a brief overview of motility disorders and the drugs approved and currently available for these indications. It also provides an evaluation of the efficacy, safety and possible mechanisms of the drugs currently under investigation for the treatment of gastroparesis, chronic diarrhea, CIC and OIC, based on animal to phase II studies. Medications with complete phase III trials are excluded from this discussion. Expert opinion Treatment of gastrointestinal motility disorders requires the understanding of the pathophysiological mechanisms, biomarkers to identify subgroups of these disorders, and robust pharmacological studies from animal to phase II studies. These are prerequisites for the development of efficacious medications and individualizing therapy in order to enhance the treatment of these patients.

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“…The development of TD-8954 (Theravance; [476,[487][488][489]) for the indication AD was terminated, but development for the treatment of gastrointestinal motility disorders is continuing (Thomson Reuters Pharma, update of May 27, 2014).…”

Section: -Ht 4 Receptor (Partial) Agonistsmentioning

confidence: 99%

Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors

Froestl

Muhs

Pfeifer

2012

JAD

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Cognitive enhancers (nootropics) are drugs to treat cognition deficits in patients suffering from Alzheimer's disease, schizophrenia, stroke, attention deficit hyperactivity disorder, or aging. Cognition refers to a capacity for information processing, applying knowledge, and changing preferences. It involves memory, attention, executive functions, perception, language, and psychomotor functions. The term nootropics was coined in 1972 when memory enhancing properties of piracetam were observed in clinical trials. In the meantime, hundreds of drugs have been evaluated in clinical trials or in preclinical experiments. To classify the compounds, a concept is proposed assigning drugs to 18 categories according to their mechanism(s) of action, in particular drugs interacting with receptors, enzymes, ion channels, nerve growth factors, re-uptake transporters, antioxidants, metal chelators, and disease-modifying drugs meaning small molecules, vaccines, and monoclonal antibodies interacting with amyloid-β and tau. For drugs, whose mechanism of action is not known, they are either classified according to structure, e.g., peptides, or their origin, e.g., natural products. The review covers the evolution of research in this field over the last 25 years.

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Discovery of TD-8954, a clinical stage 5-HT4 receptor agonist with gastrointestinal prokinetic properties

Cited by 14 publications

References 26 publications

Editorial: felcisetrag—forward movement as a novel prokinetic for gastroparesis

Editorial: felcisetrag—forward movement as a novel prokinetic for gastroparesis

Early investigational therapeutics for gastrointestinal motility disorders: from animal studies to Phase II trials

Cognitive Enhancers (Nootropics). Part 1: Drugs Interacting with Receptors

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