Thirty four N-alkylaminoacids (Arg, Trp, Nal, Pro, Hyp, L and D) and derivatives were prepared by a process that included reductive alkylation of the amino function. Both solid phase and solution synthesis was used. Title substances displayed binding activity on melanocortin receptors MC(1,3-5) reaching the low micromolar range.
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http://dx.doi.org/10.1016/s0960-894x(02)00089-6 | DOI Listing |
Biochim Biophys Acta Mol Basis Dis
January 2025
National Forensic Sciences University, Gandhinagar 382007, Gujarat, India. Electronic address:
Cancer-associated cachexia (CAC) is a debilitating condition, observed in patients with advanced stages of cancer. It is marked by ongoing weight loss, weakness, and nutritional impairment. Lower tolerance of chemotherapeutic agents and radiation therapy makes it difficult to treat CAC.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Medicinal Chemistry and the Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.
The melanocortin receptors are a class of centrally and peripherally expressed G protein-coupled receptors, of which the MC3R and MC4R subtypes are implicated in the regulation of appetite and energy homeostasis and can serve as potential therapeutic targets for disorders such as obesity and cachexia. An unbiased high-throughput mixture-based library screen was implemented to identify novel ligands with an emphasis on the identification of nanomolar-potent agonists of the mouse melanocortin-3 receptor. This screen yielded the discovery of an N-branched tricyclic guanidine scaffold (TPI2408) that contained three nanomolar potent mMC3R agonists and additional compounds that possessed antagonism for the mMC4R.
View Article and Find Full Text PDFArch Dermatol Res
January 2025
Burn and Wound Repair Center, The Third Hospital of Hebei Medical University, No. 139, Ziqiang Road, Shijiazhuang, Hebei Province, 050035, China.
This study aimed to investigate the role of transforming growth factor-beta 3 (TGF-β3) secreted by adipose-derived stem cells (ADSCs) in suppressing melanin synthesis during the wound healing process, particularly in burn injuries, and to explore the underlying mechanisms involving the cAMP/PKA signaling pathway. ADSCs were isolated from C57BL/6 mice and characterized using flow cytometry and differentiation assays. A burn injury model was established in mice, followed by UVB irradiation to induce hyperpigmentation.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Dermatology, First Affiliated Hospital of Zhengzhou University, No.1 Longhu Outer Ring Road, Jinshui District, Zhengzhou, 450052, Henan, China.
Vitiligo is a complex autoimmune disease characterized by the loss of melanocytes, leading to skin depigmentation. Despite advances in understanding its genetic and molecular basis, the precise mechanisms driving vitiligo remain elusive. Integrating multiple layers of omics data can provide a comprehensive view of disease pathogenesis and identify potential therapeutic targets.
View Article and Find Full Text PDFSci Transl Med
January 2025
Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas TX, 75390, USA.
Disruption of hypothalamic melanocortin 4 receptors (MC4Rs) causes obesity in mice and humans. Here, we investigated the transcriptional regulation of in the hypothalamus. In mice, we show that the homeodomain transcription factor Orthopedia (OTP) is enriched in MC4R neurons in the paraventricular nucleus (PVN) of the hypothalamus and directly regulates transcription.
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