Setmelanotide (trifluoroacetate salt)

Setmelanotide is a cyclic peptide agonist of melanocortin receptor 4 (MC4R). It increases cAMP production in CHO-K1 cells expressing MC4R, MC1R, MC3R, and MC5R (EC50s = 0.27, 5.8, 5.3, and 1,600 nM, respectively, for the human receptors) but not in cells expressing MC2R (EC50 = >10 µM). Setmelanotide (6.4 µmol/animal) inhibits food intake in MC3R, but not MC4R, knockout mice. It also reduces food intake and hepatosteatosis, induces weight loss, and decreases serum insulin, glucose, and leptin levels in a mouse model of diet-induced obesity when administered at a dose of 300 nmol/kg per day. Formulations containing setmelanotide have been used in chronic weight management due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor deficiency.Formal Name: cyclic (2->8)-disulfide N2-acetyl-L-arginyl-L-cysteinyl-D-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-cysteinamide, trifluoroacetate salt. Synonyms: BIM-22493, N-acetyl-RCAHFRWC-NH2, RM-493. Molecular Formula: C49H68N18O9S2 . XCF3COOH. Formula Weight: 1117.3. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: Water: soluble. SMILES: O=C([C@@H](NC([C@H](NC([C@@H](NC([C@H](NC([C@H](CSSC[C@H](NC1=O)C(N)=O)NC([C@@H](NC(C)=O)CCCNC(N)=N)=O)=O)C)=O)CC2=CN=CN2)=O)CC3=CC=CC=C3)=O)CCCNC(N)=N)N[C@H]1CC4=CNC5=CC=CC=C45.OC(C(F)(F)F)=O. InChi Code: InChI=1S/C49H68N18O9S2.C2HF3O2/c1-26-41(70)63-37(20-30-22-55-25-59-30)46(75)64-35(18-28-10-4-3-5-11-28)44(73)62-34(15-9-17-57-49(53)54)43(72)65-36(19-29-21-58-32-13-7-6-12-31(29)32)45(74)66-38(40(50)69)23-77-78-24-39(47(76)60-26)67-42(71)33(61-27(2)68)14-8-16-56-48(51)52,3-2(4,5)1(6)7/h3-7,10-13,21-22,25-26,33-39,58H,8-9,14-20,23-24H2,1-2H3,(H2,50,69)(H,55,59)(H,60,76)(H,61,68)(H,62,73)(H,63,70)(H,64,75)(H,65,72)(H,66,74)(H,67,71)(H4,51,52,56)(H4,53,54,57),(H,6,7)/t26-,33+,34+,35-,36+,37+,38+,39+,/m1./s1. InChi Key: WLNKAQFYDVNRDO-GZRAWZNHSA-N.