406953-92-2

Upstream product

• 108-24-7 acetic anhydride 
• 13139-14-5 Boc-Trp-OH 
• 71989-38-3 Fmoc-Tyr(tBu)-OH 
• 119831-72-0 Fmoc-Arg(Pbf)-OH 
• 86123-10-6 Fmoc-D-Phe-OH 
• 406953-67-1 2-(S)-(2-(R)-[2-(S)-acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-3-phenyl-propionylamino)-5-nitroguanidino-pentanoic acid [1-carbamoyl-2-(1H-indol-3-yl)-ethyl]-amide 
• 143824-78-6 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester 
• 187618-60-6 Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine 

Relevant academic research and scientific papers

Identification of tetrapeptides from a mixture based positional scanning library that can restore nM full agonist function of the L106P, I69T, I102S, A219V, C271Y, and C271R Human Melanocortin-4 Polymorphic Receptors (hMC4Rs)

Human obesity has been linked to genetic factors and single nucleotide polymorphisms (SNPs). Melanocortin-4 receptor (MC4R) SNPs have been associated with up to 6% frequency in morbidly obese children and adults. A potential therapy for individuals possessing such genetic modifications is the identification of molecules that can restore proper receptor signaling and function. These compounds could serve as personalized medications improving quality of life issues as well as alleviating diseases symptoms associated with obesity including type 2 diabetes. Several hMC4 SNP receptors have been pharmacologically characterized in vitro to have a decreased, or a lack of response, to endogenous agonists such as α-, β-, and γ2-melanocyte stimulating hormones (MSH) and adrenocorticotropin hormone (ACTH). Herein we report the use of a mixture based positional scanning combinatorial tetrapeptide library to discover molecules with nM full agonist potency and efficacy to the L106P, I69T, I102S, A219V, C271Y, and C271R hMC4Rs. The most potent compounds at all these hMC4R SNPs include Ac-His-(pI)DPhe-Tic-(pNO2)DPhe-NH2, Ac-His-(pCl)DPhe-Tic-(pNO2)DPhe-NH2, Ac-His-(pCl)DPhe-Arg- (pI)Phe-NH2, and Ac-Arg-(pCl)DPhe-Tic-(pNO2)DPhe-NH 2, revealing new ligand pharmacophore models for melanocortin receptor drug design strategies.

Melanocortin receptor ligands

Disclosed are MC-4 and/or MC-3 receptor ligands, the ligands having a structure according to Formula (I): wherein R2, R4, R4′, R5, R6, R6′, R7, R8, R8′, R9, R9′, R10, Ar, Z1, Z2, Z3, X, B, D, p, q, r and s are as described in the specification and claims, and optical isomers, diastereomers or enantiomers thereof; pharmaceutically-acceptable salts, hydrates, and biohydrolyzable esters, amides or imides thereof. Also disclosed are pharmaceutical compositions comprising the ligands of Formula (I), as well as methods of treating diseases mediate by the MC-4/MC-3 receptors, as described in the Detailed Descriptions section of the specification.