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targets (1) transporters (2)
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Identification
Name Aminolevulinic acid
Accession Number DB00855 (APRD00793, DB05277)
Type small molecule
Groups approved
Description

A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. It is used as a photochemotherapy for actinic keratosis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • 5-Aminolevulinic acid
  • ALA
  • Aminolevulinate
  • delta-Aminolevulinic acid
Brand names
  • Aladerm
  • Kerastick
  • Levulan
  • Levulan Kerastick
Brand name mixtures Not Available
Categories
  • Photosensitizing Agents
CAS number 106-60-5
Weight Average: 131.1299
Monoisotopic: 131.058243159
Chemical Formula C5H9NO3
InChI Key InChIKey=ZGXJTSGNIOSYLO-UHFFFAOYSA-N
InChI
InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)
Plain Text
IUPAC Name
5-amino-4-oxopentanoic acid
SMILES
NCC(=O)CCC(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Amino Acids
  • Carboxylic Acids and Derivatives
  • Keto-Acids
Substructures
  • Amino Acids
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Keto-Acids
  • Ketones
Pharmacology
Indication Aminolevulinic acid plus blue light illumination using a blue light photodynamic therapy illuminator is indicated for the treatment of minimally to moderately thick actinic keratoses of the face or scalp.
Pharmacodynamics The metabolism of aminolevulinic acid (ALA) is the first step in the biochemical pathway resulting in heme synthesis. Aminolevulinic acid is not a photosensitizer, but rather a metabolic precursor of protoporphyrin IX (PpIX), which is a photosensitizer. The synthesis of ALA is normally tightly controlled by feedback inhibition of the enzyme, ALA synthetase, presumably by intracellular heme levels. ALA, when provided to the cell, bypasses this control point and results in the accumulation of PpIX, which is converted into heme by ferrochelatase through the addition of iron to the PpIX nucleus.
Mechanism of action According to the presumed mechanism of action, photosensitization following application of aminolevulinic acid (ALA) topical solution occurs through the metabolic conversion of ALA to protoporphyrin IX (PpIX), which accumulates in the skin to which aminolevulinic acid has been applied. When exposed to light of appropriate wavelength and energy, the accumulated PpIX produces a photodynamic reaction, a cytotoxic process dependent upon the simultaneous presence of light and oxygen. The absorption of light results in an excited state of the porphyrin molecule, and subsequent spin transfer from PpIX to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals. Photosensitization of actinic (solar) keratosis lesions using aminolevulinic acid, plus illumination with the BLU-UTM Blue Light Photodynamic Therapy Illuminator (BLU-U), is the basis for aminolevulinic acid photodynamic therapy (PDT).
Absorption Oral bioavailability is 50-60%.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Following topical administration, synthesis into protoporphyrin IX takes place in situ in the skin.
Route of elimination Not Available
Half life Mean half-life is 0.70 ± 0.18 h after the oral dose and 0.83 ± 0.05 h after the intravenous dose.
Clearance Not Available
Toxicity Solution overdose have not been reported.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Dusa pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Powder, for solution Topical
Prices
Unit description Cost Unit
Levulan kerastick 170.25 USD each
Patents
Country Patent Number Approved Expires
United States 7723910 1999-06-17 2019-06-17
United States 5422093 1992-07-28 2009-07-28
Properties
State solid
Melting point 156-158 oC
Experimental Properties
Property Value Source
water solubility Very soluble PhysProp
logP -1.5 PhysProp
Predicted Properties
Property Value Source
water solubility 1.73e+02 g/l ALOGPS
logP -2.85 ALOGPS
logP -3.68 ChemAxon Molconvert
logS 0.12 ALOGPS
pKa 17.16 ChemAxon Molconvert
hydrogen acceptor count 4 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 80.39 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 30.45 ChemAxon Molconvert
polarizability 12.55 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ: Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006 May;7(5):392-401. Pubmed
  2. Kennedy JC, Marcus SL, Pottier RH: Photodynamic therapy (PDT) and photodiagnosis (PD) using endogenous photosensitization induced by 5-aminolevulinic acid (ALA): mechanisms and clinical results. J Clin Laser Med Surg. 1996 Oct;14(5):289-304. Pubmed
External Links
Resource Link
KEGG Compound C00430 Link_out
PubChem Compound 137 Link_out
PubChem Substance 46506856 Link_out
ChemSpider 134 Link_out
ChEBI 17549 Link_out
ChEMBL 17549 Link_out
Therapeutic Targets Database DAP000314 Link_out
PharmGKB PA10015 Link_out
Drug Product Database 0 Link_out
RxList http://www.rxlist.com/cgi/generic3/levulan.htm Link_out
Drugs.com http://www.drugs.com/cdi/aminolevulinic-acid-solution.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Aminolevulinic_acid Link_out
ATC Codes
  • L01XD04
AHFS Codes
  • 84:92.00
PDB Entries Not Available
FDA label show (195.4 KB)
MSDS show (72.5 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Delta-aminolevulinic acid dehydratase

Pharmacological action: yes
Actions: inducer
Organism class: human
UniProt ID: P13716 Link_out
Gene: ALAD Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sakai T: Biomarkers of lead exposure. Ind Health. 2000 Apr;38(2):127-42. Pubmed
  2. Vajpayee P, Tripathi RD, Rai UN, Ali MB, Singh SN: Chromium (VI) accumulation reduces chlorophyll biosynthesis, nitrate reductase activity and protein content in Nymphaea alba L. Chemosphere. 2000 Oct;41(7):1075-82. Pubmed
  3. Tomas-Zapico C, Martinez-Fraga J, Rodriguez-Colunga MJ, Tolivia D, Hardeland R, Coto-Montes A: 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. Pubmed
  4. Frere F, Schubert WD, Stauffer F, Frankenberg N, Neier R, Jahn D, Heinz DW: Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism. J Mol Biol. 2002 Jul 5;320(2):237-47. Pubmed
  5. Flora SJ, Kannan GM, Pant BP, Jaiswal DK: Combined administration of oxalic acid, succimer and its analogue for the reversal of gallium arsenide-induced oxidative stress in rats. Arch Toxicol. 2002 Jun;76(5-6):269-76. Epub 2002 Apr 23. Pubmed
  6. Akagi R, Yasui Y, Harper P, Sassa S: 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. Pubmed
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Terada T, Sawada K, Irie M, Saito H, Hashimoto Y, Inui K: Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflugers Arch. 2000 Sep;440(5):679-84. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: inhibitor

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Terada T, Sawada K, Irie M, Saito H, Hashimoto Y, Inui K: Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflugers Arch. 2000 Sep;440(5):679-84. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 11:19

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.