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]
------------------------------------------------------------------------------------

ATC Code

D02BB02: Afamelanotide

D02BB: Protectives against UV-radiation for systemic use

D02B: PROTECTIVES AGAINST UV-RADIATION

D02: EMOLLIENTS AND PROTECTIVES

D: DERMATOLOGICALS

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 5

Molecular Weight (mw)

1646.8

Logarithm of the Partition Coefficient (xlogp)

-3.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

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
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 Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

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

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

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.