Details of the Drug

General Information of Drug (ID: DMPVRN9)

• Drug Name: Setmelanotide
• Synonyms: RM-493; UNII-N7T15V1FUY; BIM-22493; N7T15V1FUY; 920014-72-8; Setmelanotide [USAN:INN]; GTPL9272; CHEMBL3301624; CS-6399; DB11700; HY-19870; L-Cysteinamide, N2-acetyl-L-arginyl-L-cysteinyl-D-alanyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-, cyclic (2-> 8)-disulfide; (4R,7S,10S,13R,16S,19R,22R)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-13-benzyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-19-methyl-6,9,12,15,18,21-hexaoxo-1,2-d

Indication

Disease Entry	ICD 11	Status	REF
Obesity	5B81	Approved	[1]
Bardet biedl syndrome	5A61.0	Phase 3	[2]
Prader-Willi syndrome	LD90.3	Phase 2	[3]
Diabetic complication	5A2Y	Preclinical	[4]

• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 1117.3
  Topological Polar Surface Area (xlogp); -2.5
  Rotatable Bond Count (rotbonds); 18
  Hydrogen Bond Donor Count (hbonddonor); 15
  Hydrogen Bond Acceptor Count (hbondacc); 14
• ADMET Property:
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 8 h [5]
  Clearance: The clearance of drug is 4.86 L/h [5]
  Elimination: A 3mg subcutaneous dose of setmelanotide is 39% eliminated in the urine as the unchanged parent compound [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 11 hours [5]
  Metabolism: The drug is metabolized to small peptides and amino acids [5]
  Vd: The volume of distribution (Vd) of drug is 48.7 L [5]
• Chemical Identifiers:
  Formula: C49H68N18O9S2
  IUPAC Name: (4R,7S,10S,13R,16S,19R,22R)-22-[[(2S)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-13-benzyl-10-[3-(diaminomethylideneamino)propyl]-16-(1H-imidazol-5-ylmethyl)-7-(1H-indol-3-ylmethyl)-19-methyl-6,9,12,15,18,21-hexaoxo-1,2-dithia-5,8,11,14,17,20-hexazacyclotricosane-4-carboxamide
  Canonical SMILES: C[C@@H]1C(=O)N[C@H](C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCN=C(N)N)NC(=O)C)C(=O)N)CC2=CNC3=CC=CC=C32)CCCN=C(N)N)CC4=CC=CC=C4)CC5=CN=CN5
  InChI: InChI=1S/C49H68N18O9S2/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/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)/t26-,33+,34+,35-,36+,37+,38+,39+/m1/s1
  InChIKey: HDHDTKMUACZDAA-PHNIDTBTSA-N
• Cross-matching ID:
  PubChem CID: 11993702
  CAS Number: 920014-72-8
  DrugBank ID: DB11700
  TTD ID: D0YP7B
  ACDINA ID: D01425

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Melanocortin receptor 4 (MC4R)	TTD0CIQ	MC4R_HUMAN	Agonist	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Obesity
• ICD Disease Classification: 5B81

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Melanocortin receptor 4 (MC4R)	DTT	MC4R	5.64E-01	-0.04	-0.18

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Benzyl alcohol	E00010	244	Antimicrobial preservative; Solvent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Phenol	E00038	996	Antimicrobial preservative
Carboxymethylcellulose sodium	E00621	Not Available	Adsorbent; Binding agent; Disintegrant; Emulsifying agent; Suspending agent; Viscosity-controlling agent
Edetate disodium	E00186	8759	Complexing agent
Water	E00035	962	Solvent
N-(carbonyl-methoxypolyethylene glycol 2000)-1	E00685	86278269	Other agent

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Setmelanotide 10 mg/ml Injection	10 mg/ml	Injection	Subcutaneous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [2] ClinicalTrials.gov (NCT03746522) Setmelanotide (RM-493), Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alstrom Syndrome (AS) Patients With Moderate to Severe Obesity. U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] 2011 Pipeline of Ipsen.
• [5] FDA Approved Drug Products: Imcivree (Setmelanotide) Subcutaneous Injection
• [6] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [8] Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26.
• [9] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [10] Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology. 2015 Jul;40(8):1856-65.
• [11] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [12] The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II (MTII), against binge-like ethanol drinking are facilitated by deletion of the MC3 receptor in mice. Neuropeptides. 2014 Feb;48(1):47-51.