ArticleJournal of cachexia, sarcopenia and muscle2020
Characterization of the cellular transport mechanisms for the anti-cachexia candidate compound TCMCB07.
Article in Journal of cachexia, sarcopenia and muscle, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Development of a Therapeutic Peptide for Cachexia Suggests a Platform Approach for Drug-like Peptides.ACS pharmacology & translational science · 2022Article
- Pharmacokinetics and safety of TCMCB07, a melanocortin-4 antagonist peptide in dogs.Pharmacology research & perspectives · 2021Article
- Characterization of the cellular transport mechanisms for the anti-cachexia candidate compound TCMCB07.Journal of cachexia, sarcopenia and muscle · 2020Article
- Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia.Journal of veterinary internal medicineArticle
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCachexia is a debilitating, life-threatening condition whose pathology includes reduced food intake accompanied by hypermetabolism, leading to a catabolic state. The hypothalamic melanocortin system is a critical regulator of metabolic rate with effects being mediated through the melanocortin-4 receptor (MC4R). MC4R activation is also critical to the initiation and maintenance of cachexia. A major problem in the design of anti-cachexia drugs has been the need to cross the blood-brain barrier to access the metabolic rate-controlling centres in the hypothalamus. The overwhelming majority of anti-cachexia drugs are only effective when administered intracerebroventricularly. TCMCB07 is a cyclic nonapeptide peptide MC4R antagonist with parenteral anti-cachexia activity in both small and large animal models. This suggests it can cross the blood-brain barrier. The aim of this study was to examine potential transport mechanisms of TCMCB07 furthering its preclinical development for subsequent studies in humans.
methodsIn vitro studies were performed in transporter-transfected cells to study whether or not TCMCB07 was an inhibitor as well as substrate for OATP1A2, OATP1B1, OATP1B3, OATP2B1, OCT2, OAT1, OAT3, MATE1, MATE2-K, P-gp (MDR1), and BCRP. In vivo mass balance studies were also performed in mice to evaluate the absorption and disposition of TCMCB07 after oral and intravenous bolus administrations.
resultsTCMCB07 inhibited the uptake of prototypical substrates in cells transfected with OATP1A2 (IC
conclusionsOATP1A2 is the transporter responsible for the oral absorption of TCMCB07 in the intestine and for its pharmacologic response in the brain.
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