Details of the Drug

General Information of Drug (ID: DMVWHTG)

• Drug Name: Afamelanotide
• Synonyms: [Nle4,dPhe7]alpha-MSH; alpha-NDP-MSH; NDP-MSH

Indication

Disease Entry	ICD 11	Status	REF
Erythropoietic porphyrias	5C58.12	Approved	[1]
Erythropoietic protoporphyria	5C58.12	Approved	[2]
Vitiligo	ED63.0	Phase 2	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 5:
  Molecular Weight (mw); 1646.8
  Logarithm of the Partition Coefficient (xlogp); -3.5
  Rotatable Bond Count (rotbonds); 51
  Hydrogen Bond Donor Count (hbonddonor); 23
  Hydrogen Bond Acceptor Count (hbondacc); 22
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 138.9 +/- 42.6 mcgh/L [4]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3.7 +/- 1.3 mcg/L [4]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 36 h [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 30 minutes [4]
  Metabolism: The drug is metabolized via serum and proteolytic enzyme [5]
  Vd: The volume of distribution (Vd) of drug is 0.54 L/kg [5]
• Chemical Identifiers:
  Formula: C78H111N21O19
  IUPAC Name: (4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[(2S)-2-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
  Canonical SMILES: CCCC[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CN=CN1)C(=O)N[C@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N5CCC[C@H]5C(=O)N[C@@H](C(C)C)C(=O)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CC=C(C=C6)O)NC(=O)[C@H](CO)NC(=O)C
  InChI: InChI=1S/C78H111N21O19/c1-5-6-19-52(91-75(116)61(41-101)97-72(113)57(34-46-24-26-49(103)27-25-46)94-74(115)60(40-100)88-44(4)102)68(109)92-54(28-29-64(105)106)70(111)96-59(36-48-38-83-42-87-48)73(114)93-56(33-45-16-8-7-9-17-45)71(112)90-53(22-14-31-84-78(81)82)69(110)95-58(35-47-37-85-51-20-11-10-18-50(47)51)67(108)86-39-63(104)89-55(21-12-13-30-79)77(118)99-32-15-23-62(99)76(117)98-65(43(2)3)66(80)107/h7-11,16-18,20,24-27,37-38,42-43,52-62,65,85,100-101,103H,5-6,12-15,19,21-23,28-36,39-41,79H2,1-4H3,(H2,80,107)(H,83,87)(H,86,108)(H,88,102)(H,89,104)(H,90,112)(H,91,116)(H,92,109)(H,93,114)(H,94,115)(H,95,110)(H,96,111)(H,97,113)(H,98,117)(H,105,106)(H4,81,82,84)/t52-,53-,54-,55-,56+,57-,58-,59-,60-,61-,62-,65-/m0/s1
  InChIKey: UAHFGYDRQSXQEB-LEBBXHLNSA-N
• Cross-matching ID:
  PubChem CID: 16197727
  CAS Number: 75921-69-6
  DrugBank ID: DB04931
  TTD ID: D0V2OX
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Melanocortin receptor 1 (MC1R)	TT0MV2T	MSHR_HUMAN	Modulator	[1]

Molecular Expression Atlas of This Drug

• The Studied Disease: Erythropoietic porphyrias
• ICD Disease Classification: 5C58.12

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Melanocortin receptor 1 (MC1R)	DTT	MC1R	1.44E-06	0.41	2.15

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] Afamelanotide FDA Label
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] EMA Approved Drugs: Afamelanotide
• [5] Ghosal A, Chowdhury SK, Tong W, Hapangama N, Yuan Y, Su AD, Zbaida S: Identification of human liver cytochrome P450 enzymes responsible for the metabolism of lonafarnib (Sarasar). Drug Metab Dispos. 2006 Apr;34(4):628-35. doi: 10.1124/dmd.105.007906. Epub 2006 Jan 27.