setmelanotide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
peptides and glycopeptides 5416 920014-72-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • setmelanotide
  • setmelanotide hydrochloride
  • setmelanotide acetate
  • imcivree
  • RM-493
Setmelanotide is an 8 amino acid cyclic peptide analog of endogenous melanocortin peptide alpha-MSH (alpha-melanocyte stimulating hormone). It is a melanocortin 4 (MC4) receptor agonist, with 20-fold less activity at the melanocortin 3 (MC3) and melanocortin 1 (MC1) receptors.
  • Molecular weight: 1117.32
  • Formula: C49H68N18O9S2
  • CLOGP: -2.65
  • LIPINSKI: 3
  • HAC: 27
  • HDO: 15
  • TPSA: 444.16
  • ALOGS: -4.59
  • ROTB: 18

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 -0.732 High 0.84
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.871 High 0.84
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 0.514 10^-6 cm/s High 0.84
dh-clint Dog hepatocyte intrinsic clearance 1.528 uL/min/10^6 cells High 0.84
dppb Dog plasma protein binding (% unbound) 82.420 % High 0.84
fcs-ppb Fetal calf serum protein binding (% unbound) 45.640 % High 0.84
herg hERG pIC50 4.507 pIC50 High 0.84
hh-clint Human hepatocyte intrinsic clearance 4.009 uL/min/10^6 cells High 0.84
hlm-clint Human liver microsomal intrinsic clearance 3.540 uL/min/mg protein High 0.84
hppb Human plasma protein binding (% unbound) 78.250 % High 0.84
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,CDK5,CDK9,EIF2AK3,ERBB2,GRK2,ITK,MAPK10,MAPK7,NTRK2,PDK1,PDK2,PDK4,PRKDC,TEK 18
kinase-selectivity-class GRK2 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.384 High 0.84
mh-clint Mouse hepatocyte intrinsic clearance 19.724 High 0.84
mppb Mouse plasma protein binding (% unbound) 75.930 High 0.84
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.871 High 0.84
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 80.330 % High 0.84
rh-clint Rat hepatocyte intrinsic clearance 5.164 uL/min/10^6 cells High 0.84
rh-fuinc Rat hepatocyte fraction unbound in incubation 80.510 % High 0.84
rppb Rat plasma protein binding (% unbound) 67.830 % High 0.84
solubility-dd Solubility at pH 7.4 in DMSO 891.251 uM High 0.84

Approvals:

DateAgencyCompanyOrphan
Nov. 25, 2020 FDA RHYTHM PHARMACEUTICALS INC
Nov. 19, 2018 EMA Rhythm Pharmaceuticals Limited

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Skin hyperpigmentation 92.68 47.37 15 144 6836 90621452

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Skin hyperpigmentation 90.87 51.10 16 248 8680 110580355

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC A08AA12 ALIMENTARY TRACT AND METABOLISM
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
ANTIOBESITY PREPARATIONS, EXCL. DIET PRODUCTS
Centrally acting antiobesity products
FDA EPC N0000193940 Melanocortin 4 Receptor Agonist
FDA MoA N0000193941 Melanocortin 4 Receptor Agonists
CHEBI has role CHEBI:74518 anti-obesity agent

Related Drugs by ATC class:

A08AA Centrally acting antiobesity products 15 drugs

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
BardetBiedl syndrome indication 5619004 DOID:1935
Obesity indication 414916001 DOID:9970
Pro-opiomelanocortin (POMC) deficiency indication 702949005
Leptin receptor (LEPR) deficiency indication 785722006




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS Nov. 25, 2027 INDICATED FOR CHRONIC WEIGHT MANAGEMENT IN ADULT AND PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WITH OBESITY DUE TO PROOPIOMELANOCORTIN (POMC), PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 1 (PCSK1), OR LEPTIN RECEPTOR (LEPR) DEFICIENCY CONFIRMED BY GENETIC TESTING DEMONSTRATING VARIANTS IN POMC, PCSK1, OR LEPR GENES THAT ARE INTERPRETED AS PATHOGENIC, LIKELY PATHOGENIC, OR OF UNCERTAIN SIGNIFICANCE (VUS)
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS Dec. 20, 2027 NEW PATIENT POPULATION
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS March 19, 2029 TO REDUCE EXCESS BODY WEIGHT AND MAINTAIN WEIGHT REDUCTION LONG TERM IN ADULTS AND PEDIATRIC PATIENTS AGED 4 YEARS AND OLDER WITH ACQUIRED HYPOTHALAMIC OBESITY
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS June 16, 2029 FOR CHRONIC WEIGHT MANAGEMENT IN ADULT AND PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER WITH MONOGENIC OR SYNDROMIC OBESITY DUE TO BARDET-BIEDL SYNDROME (BBS)
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS Dec. 20, 2031 TO REDUCE EXCESS BODY WEIGHT AND MAINTAIN WEIGHT REDUCTION LONG TERM IN PEDIATRIC PATIENTS AGED 2 YEARS TO LESS THAN 6 YEARS WITH SYNDROMIC OR MONOGENIC OBESITY DUE TO BARDET-BIEDL SYNDROME (BBS)
EQ 10MG BASE/ML (EQ 10MG BASE/ML) IMCIVREE RHYTHM N213793 Nov. 25, 2020 RX SOLUTION SUBCUTANEOUS Dec. 20, 2031 TO REDUCE EXCESS BODY WEIGHT AND MAINTAIN WEIGHT REDUCTION LONG TERM IN PEDIATRIC PATIENTS AGED 2 YEARS TO LESS THAN 6 YEARS WITH SYNDROMIC OR MONOGENIC OBESITY DUE TO PRO-OPIOMELANOCORTIN (POMC), PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 1 (PCSK1), OR LEPTIN RECEPTOR (LEPR) DEFICIENCY AS DETERMINED BY AN FDA-APPROVED TEST DEMONSTRATING VARIANTS IN POMC, PCSK1, OR LEPR GENES THAT ARE INTERPRETED AS PATHOGENIC, LIKELY PATHOGENIC, OR OF UNCERTAIN SIGNIFICANCE (VUS)

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Melanocortin receptor 4 GPCR AGONIST Kd 8.68 DRUG LABEL DRUG LABEL
Melanocortin receptor 5 GPCR AGONIST Ki 6.37 IUPHAR
Melanocortin receptor 3 GPCR AGONIST Ki 8 IUPHAR
Melanocyte-stimulating hormone receptor GPCR AGONIST Ki 8.41 IUPHAR
Melanocortin receptor 4 GPCR AGONIST Ki 8.57 IUPHAR

External reference:

IDSource
D11927 KEGG_DRUG
N7T15V1FUY UNII
2324799-41-7 SECONDARY_CAS_RN
1504602-49-6 SECONDARY_CAS_RN
C4279595 UMLSCUI
CHEBI:755301 CHEBI
CHEMBL3301624 ChEMBL_ID
11993702 PUBCHEM_CID
DB11700 DRUGBANK_ID
CHEMBL4594386 ChEMBL_ID
CHEMBL4650273 ChEMBL_ID
10011 INN_ID
C579663 MESH_SUPPLEMENTAL_RECORD_UI
9272 IUPHAR_LIGAND_ID
1137634006 SNOMEDCT_US
1137658005 SNOMEDCT_US
1137662004 SNOMEDCT_US
4042518 VANDF
341288 MMSL
39054 MMSL
d09689 MMSL
018576 NDDF
018577 NDDF
2469247 RXNORM
N7T15V1FUY INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Imcivree HUMAN PRESCRIPTION DRUG LABEL 1 72829-010 SOLUTION 10 mg SUBCUTANEOUS NDA 28 sections