ArticleJournal of cachexia, sarcopenia and muscle2011
The orally active melanocortin-4 receptor antagonist BL-6020/979: a promising candidate for the treatment of cancer cachexia.
Article in Journal of cachexia, sarcopenia and muscle, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Low skeletal muscle mass and post-operative complications after surgery for liver malignancies: a meta-analysis.Langenbeck's archives of surgery · 2022Pooled it
- Preoperative computed tomography-assessed sarcopenia as a predictor of complications and long-term prognosis in patients with colorectal cancer: a systematic review and meta-analysis.Langenbeck's archives of surgery · 2021Pooled it
- Cancer cachexia: molecular basis and therapeutic advances.Signal transduction and targeted therapy · 2026Review
- The relationship between sarcopenia and breast cancer: mechanistic pathways and clinical relevance.Frontiers in cell and developmental biology · 2026Review
- Melanocortin-4 receptor antagonist TCMCB07 alleviates chemotherapy-induced anorexia and weight loss in rats.The Journal of clinical investigation · 2024Article
- Immunoregulation in cancer-associated cachexia.Journal of advanced research · 2024Review
- Systemic Reprogramming of Endothelial Cell Signaling in Metastasis and Cachexia.Physiology (Bethesda, Md.) · 2023Review
- The differential effects of sarcopenia and cachexia on overall survival for pancreatic ductal adenocarcinoma patients following pancreatectomy: A retrospective study based on a large population.Cancer medicine · 2023Article
- Interstitial Brachytherapy for Hepatocellular Carcinoma: Analysis of Prognostic Factors for Overall Survival and Progression-Free Survival and Application of a Risk Stratification Model.Digestive diseases (Basel, Switzerland) · 2023Article
- Benefit of laparoscopic compared to standard open gastric cancer surgery for sarcopenic patients: a propensity score-matching analysis.Surgical endoscopy · 2022Article
- Review
- Emerging signaling mediators in the anorexia-cachexia syndrome of cancer.Trends in cancer · 2022Review
- Assessment of sarcopenia as a predictor of poor overall survival for advanced non-small-cell lung cancer patients receiving salvage anti-PD-1 immunotherapy.Annals of translational medicine · 2021Article
- Article
- Pharmacokinetics and safety of TCMCB07, a melanocortin-4 antagonist peptide in dogs.Pharmacology research & perspectives · 2021Article
- Association between temporal muscle thickness and clinical outcomes in patients with newly diagnosed glioblastoma.Journal of cancer research and clinical oncology · 2021Article
- Asperuloside Enhances Taste Perception and Prevents Weight Gain in High-Fat Fed Mice.Frontiers in endocrinology · 2021Article
- Characterization of the cellular transport mechanisms for the anti-cachexia candidate compound TCMCB07.Journal of cachexia, sarcopenia and muscle · 2020Article
- Melanocortin-4 receptor antagonist TCMCB07 ameliorates cancer- and chronic kidney disease-associated cachexia.The Journal of clinical investigation · 2020Article
- Cancer Cachexia: Definition, Staging, and Emerging Treatments.Cancer management and research · 2020Review
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUnder physiological conditions, the melanocortin system is a crucial part of the complex network regulating food intake and energy expenditure. In pathological states, like cachexia, these two parameters are deregulated, i.e., food intake is decreased and energy expenditure is increased-a vicious combination leading to catabolism. Agouti-related protein (AgRP), the endogenous antagonist at the melanocortin-4 receptor (MC-4R), was found to increase food intake and to reduce energy expenditure. This qualifies MC-4R blockade as an attractive mode of action for the treatment of cachexia. Based on this rationale, a novel series of small-molecule MC-4R antagonists was designed, from which the orally active compound BL-6020/979 (formerly known as SNT207979) emerged as the first promising development candidate showing encouraging pre-clinical efficacy and safety properties which are presented here. METHODS AND
resultsBL-6020/979 is an orally available, selective and potent MC-4R antagonist with a drug-like profile. It increased food intake and decreased energy expenditure in healthy wild-type but not in MC-4R deficient mice. More importantly, it ameliorated cachexia-like symptoms in the murine C26 adenocarcinoma model; with an effect on body mass and body composition and on the expression of catabolic genes. Moreover, BL-6020/979 showed antidepressant-like properties in the chronic mild stress model in rats and exhibits a favorable safety profile.
conclusionThe properties of BL-6020/979 demonstrated in animal models and presented here make it a promising candidate suitable for further development towards a first-in-class treatment option for cachexia that potentially opens up the opportunity to treat two hallmarks of the disease, i.e., decreased food intake and increased energy expenditure, with one drug.
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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.