HS-014 (trifluoroacetate salt)

HS-014 is an antagonist of melanocortin receptor 4 (MC4R, Ki = 3.16 nM). It is selective for MC4R over MC1R, MC3R, and MC5R (Kis = 108, 54.4, and 694 nM, respectively). HS-014 inhibits cAMP accumulation induced by alpha-melanocyte-stimulating hormone (alpha-MSH) in COS-1 cells expressing MC4R in a concentration-dependent manner. It increases food intake in free-feeding rats when administered intracerebroventricularly at doses of 1 or 3 nmol/animal. Intracerebroventricular administration of HS-014 (0.008 ng/animal) increases the latency to tail withdrawal in the tail-flick test, as well as inhibits morphine withdrawal-induced decreases in the latency to tail withdrawal in the tail-flick test, in rats. It reduces immobility time in the forced swim test, as well as increases time in the open area and reduces the number of droppings in an open field test, in rats when administered at a dose of 100 µg/animal.Formal Name: cyclic (1->8)-disulfide N-acetyl-L-cysteinyl-L-alpha-glutamyl-L-histidyl-3-(2-naphthalenyl)-D-alanyl-L-arginyl-L-tryptophylglycyl-L-cysteinyl-L-prolyl-L-prolyl-L-lysyl-L-alpha-asparagine, trifluoroacetate salt. Synonyms: Cyclic [Ac-Cys11, D-Nal14, Cys18, Asp-NH2]-beta-MSH(11-22). Molecular Formula: C71H94N20O17S2 . XCF3COOH. Formula Weight: 1563.8. Purity: >98%. Formulation: (Request formulation change), A solid. Peptide Sequence: Ac-CEHXRWGCPPKD-NH2 (X = 3-(2-naphthyl)-alanine). Solubility: DMSO: Soluble: >10 mg/ml, PBS (pH 7.2): Soluble: >10 mg/ml. SMILES: O=C([C@@H](NC([C@H](NC([C@@H](NC([C@@H](NC([C@H](CSSC[C@H](NC(CNC1=O)=O)C(N2[C@@H](CCC2)C(N3[C@@H](CCC3)C(N[C@@H](CCCCN)C(N[C@H](C(N)=O)CC(O)=O)=O)=O)=O)=O)NC(C)=O)=O)CCC(O)=O)=O)CC4=CN=CN4)=O)CC5=CC6=C(C=CC=C6)C=C5)=O)CCCNC(N)=N)N[C@H]1CC7=CNC8=CC=CC=C78.O=C(O)C(F)(F)F. InChi Code: InChI=1S/C71H94N20O17S2.C2HF3O2/c1-38(92)81-53-35-109-110-36-54(69(107)91-26-10-18-56(91)70(108)90-25-9-17-55(90)68(106)85-46(15-6-7-23-72)62(100)86-49(60(73)98)31-59(96)97)82-57(93)34-79-61(99)51(29-42-32-78-45-14-5-4-13-44(42)45)88-63(101)47(16-8-24-77-71(74)75)83-65(103)50(28-39-19-20-40-11-2-3-12-41(40)27-39)87-66(104)52(30-43-33-76-37-80-43)89-64(102)48(84-67(53)105)21-22-58(94)95,3-2(4,5)1(6)7/h2-5,11-14,19-20,27,32-33,37,46-56,78H,6-10,15-18,21-26,28-31,34-36,72H2,1H3,(H2,73,98)(H,76,80)(H,79,99)(H,81,92)(H,82,93)(H,83,103)(H,84,105)(H,85,106)(H,86,100)(H,87,104)(H,88,101)(H,89,102)(H,94,95)(H,96,97)(H4,74,75,77),(H,6,7)/t46-,47-,48-,49-,50+,51-,52-,53-,54-,55-,56-,/m0./s1. InChi Key: XFWXDSGIBQHHGQ-FNAFJDLNSA-N.