Details of the Drug

General Information of Drug (ID: DMS4BLQ)

• Drug Name: Aminolevulinic acid hci
• Synonyms: Aminolevulinic acid; 5-Aminolevulinic acid; 5-Amino-4-oxopentanoic acid; 106-60-5; 5-Aminolevulinate; delta-aminolevulinic acid; Pentanoic acid, 5-amino-4-oxo-; Aladerm; 5-Amino-4-oxovaleric acid; Kerastick; Ameluz; Aminolevulinate; 5-ALA; delta-ALA; 5-Amino-4-oxopentanoate; 5-amino-levulinate; 5-amino-levulinic acid; 5-amino-4-oxo-pentanoic acid; CCRIS 8958; UNII-88755TAZ87; EINECS 203-414-1; Levulinic acid, 5-amino-; CHEMBL601; 4-oxo-5-amino-pentanoic acid; CHEBI:17549; ZGXJTSGNIOSYLO-UHFFFAOYSA-N; 88755TAZ87; Levulan (TN)

Indication

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[1], [2]
Actinic keratosis	EK90.0	Approved	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 1:
  Molecular Weight (mw); 131.13
  Topological Polar Surface Area (xlogp); -3.8
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  Bioavailability: The bioavailability of drug is 50-60% [4]
  Clearance: The drug present in the plasma can be removed from the body at the rate of 1.88 mL/min/kg [5]
  Half-life: The concentration or amount of drug in body reduced by one-half in 0.70 +/-0.18 hours [5]
  Metabolism: The drug is metabolized via skin [4]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.88% [5]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.12 L/kg [5]
• Chemical Identifiers:
  Formula: C5H9NO3
  IUPAC Name: 5-amino-4-oxopentanoic acid
  Canonical SMILES: C(CC(=O)O)C(=O)CN
  InChI: InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)
  InChIKey: ZGXJTSGNIOSYLO-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 137
  ChEBI ID: CHEBI:17549
  CAS Number: 106-60-5
  DrugBank ID: DB00855
  TTD ID: D0Y7ZD
  VARIDT ID: DR00057
  INTEDE ID: DR0088

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Delta-aminolevulinic acid dehydratase (ALAD)	TTJHKYD	HEM2_HUMAN	Inhibitor	[6], [7], [8]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Peptide transporter 2 (SLC15A2)	DT8QKNP	S15A2_HUMAN	Substrate	[9]
Proton-coupled amino acid transporter 1 (SLC36A1)	DT48WEM	S36A1_HUMAN	Substrate	[10]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[11]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Porphobilinogen synthase (ALAD) Main DME	DETBNY4	HEM2_HUMAN	Substrate	[12]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 4784).
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [5] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [6] Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9.
• [7] Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands. Int J Biochem Cell Biol. 2002 May;34(5):544-53.
• [8] A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity. Br J Haematol. 1999 Sep;106(4):931-7.
• [9] PEPT2-mediated transport of 5-aminolevulinic acid and carnosine in astrocytes. Brain Res. 2006 Nov 29;1122(1):18-23.
• [10] Delta-aminolevulinic acid is a substrate for the amino acid transporter SLC36A1 (hPAT1). Br J Pharmacol. 2010 Mar;159(6):1339-53.
• [11] Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine. J Pharmacol Exp Ther. 2010 Jan;332(1):220-8.
• [12] Modifying effects of delta-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicol Lett. 2018 Oct 1;295:351-356.
• [13] Interactions of amoxicillin and cefaclor with human renal organic anion and peptide transporters. Drug Metab Dispos. 2006 Apr;34(4):547-55.
• [14] Peptide transporter substrate identification during permeability screening in drug discovery: comparison of transfected MDCK-hPepT1 cells to Caco-2 cells. Arch Pharm Res. 2007 Apr;30(4):507-18.
• [15] Several hPepT1-transported drugs are substrates of the Escherichia coli proton-coupled oligopeptide transporter YdgR. Res Microbiol. 2017 Jun;168(5):443-449.
• [16] High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
• [17] The intestinal H+/peptide symporter PEPT1: structure-affinity relationships. Eur J Pharm Sci. 2004 Jan;21(1):53-60.
• [18] Three-dimensional quantitative structure-activity relationship analyses of beta-lactam antibiotics and tripeptides as substrates of the mammalian H+/peptide cotransporter PEPT1. J Med Chem. 2005 Jun 30;48(13):4410-9.
• [19] Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm Res. 1999 Jan;16(1):55-61.
• [20] Transport characteristics of a novel peptide transporter 1 substrate, antihypotensive drug midodrine, and its amino acid derivatives. J Pharmacol Exp Ther. 2006 Jul;318(1):455-60.
• [21] Ethanol inhibits functional activity of the human intestinal dipeptide transporter hPepT1 expressed in Xenopus oocytes. Alcohol Clin Exp Res. 2008 May;32(5):777-84.
• [22] The oligopeptide transporter 2-mediated reabsorption of entecavir in rat kidney. Eur J Pharm Sci. 2014 Feb 14;52:41-7.
• [23] Species Differences in Human and Rodent PEPT2-Mediated Transport of Glycylsarcosine and Cefadroxil in Pichia Pastoris Transformants. Drug Metab Dispos. 2017 Feb;45(2):130-136.
• [24] Valacyclovir: a substrate for the intestinal and renal peptide transporters PEPT1 and PEPT2. Biochem Biophys Res Commun. 1998 May 19;246(2):470-5.
• [25] Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41.
• [26] Transport of amino acids and GABA analogues via the human proton-coupled amino acid transporter, hPAT1: characterization of conditions for affinity and transport experiments in Caco-2 cells. Eur J Pharm Sci. 2008 Sep 2;35(1-2):86-95.
• [27] PAT1 (SLC36A1) shows nuclear localization and affects growth of smooth muscle cells from rats. Am J Physiol Endocrinol Metab. 2014 Jan 1;306(1):E65-74.
• [28] Indirect regulation of the intestinal H+-coupled amino acid transporter hPAT1 (SLC36A1). J Cell Physiol. 2005 Aug;204(2):604-13.
• [29] Intestinal gaboxadol absorption via PAT1 (SLC36A1): modified absorption in vivo following co-administration of L-tryptophan. Br J Pharmacol. 2009 Aug;157(8):1380-9.
• [30] Rectal absorption of vigabatrin, a substrate of the proton coupled amino acid transporter (PAT1, Slc36a1), in rats. Pharm Res. 2012 Apr;29(4):1134-42.
• [31] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.