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Showing drug card for Aminolevulinic acid (DB00855)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:05
Primary Accession Number DB00855
Secondary Accession Number
  • APRD00793
Name Aminolevulinic acid
Drug Type
  • Approved
  • Small Molecule
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]
Synonyms
  1. ALA
  2. Aminolevulinate
  3. delta-Aminolevulinic acid
Brand Names
  1. Aladerm
  2. Kerastick
  3. Levulan
  4. Levulan Kerastick
Brand Mixtures Not Available
Chemical IUPAC Name 5-amino-4-oxopentanoic acid
Chemical Formula C5H9NO3
Chemical Structure Structure
CAS Registry Number 106-60-5
InChI Identifier InChI=1/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)/f/h8H
InChI Key ZGXJTSGNIOSYLO-FZOZFQFYCQ
KEGG Drug Not Available
KEGG Compound C00430 Link Image
PubChem Compound 137 Link Image
PubChem Substance 3719 Link Image
ChEBI ID 17549 Link Image
PharmGKB ID PA10015 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic3/levulan.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Aminolevulinic_acid Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 131.1299
Monoisotopic Molecular Weight 131.0582
State Solid
Melting Point 156-158 oC
Experimental Water Solubility Very soluble Source: PhysProp
Predicted Water Solubility 1.73e+02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.5 Source: PhysProp
Predicted LogP -2.84 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS 0.12 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES NCC(=O)CCC(O)=O
Canonical SMILES NCC(=O)CCC(O)=O
Drug Category
  • Photosensitizing Agents
ATC Codes
AHFS Codes
  • 84:92.00
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.
Pharmacology 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%.
Toxicity Solution overdose have not been reported.
Protein Binding Not Available
Biotransformation Following topical administration, synthesis into protoporphyrin IX takes place in situ in the skin.
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.
Dosage Forms
Form Route
Powder, for solution Topical
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  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 Link Image]
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Targets
  1. Delta-aminolevulinic acid dehydratase
Drug Target 1 [top]
Target 1 ID 56
Target 1 Name Delta-aminolevulinic acid dehydratase
Target 1 Synonyms
  1. ALADH
  2. EC 4.2.1.24
  3. Porphobilinogen synthase
Target 1 Gene Name ALAD
Target 1 Protein Sequence >Delta-aminolevulinic acid dehydratase 
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
LEAMTAFRRAGADIIITYYTPQLLQWLKEE
Target 1 Number of Residues 335
Target 1 Molecular Weight 36295
Target 1 Theoretical pI 6.78
Target 1 GO Classification
Function
catalytic activity
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
porphobilinogen synthase activity
Process
physiological process
metabolism
cellular metabolism
heterocycle metabolism
porphyrin metabolism
porphyrin biosynthesis
heme biosynthesis
Component
Not Available
Target 1 General Function Coenzyme transport and metabolism
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
Porphyrin and chlorophyll metabolism map00860 Link Image
Target 1 Reactions
  • 2 5-aminolevulinate = porphobilinogen + 2 H2O
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 178329 Link Image
Target 1 UniProtKB/Swiss-Prot ID P13716 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HEM2_HUMAN Link Image
Target 1 PDB ID 1E51 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location Not Available
Target 1 Gene Sequence >993 bp 
ATGCAGCCCCAGTCCGTTCTGCACAGCGGCTACTTCCACCCACTACTTCGGGCCTGGCAG
ACAGCCACCACCACCCTCAATGCCTCCAACCTCATCTACCCCATCTTTGTCACGGATGTT
CCTGATGACATACAGCCTATCACCAGCCTCCCAGGAGTGGCCAGGTATGGTGTGAAGCGG
CTGGAAGAGATGCTGAGGCCCTTGGTGGAAGAGGGCCTACGCTGTGTCTTGATCTTTGGC
GTCCCCAGCAGAGTTCCCAAGGACGAGCGGGGTTCCGCAGCTGACTCCGAGGAGTCCCCA
GCTATTGAGGCAATCCATCTGTTGAGGAAGACCTTCCCCAACCTCCTGGTGGCCTGTGAT
GTCTGCCTGTGTCCCTACACCTCCCATGGTCACTGCGGGCTCCTGAGTGAAAACGGAGCA
TTCCGGGCTGAGGAGAGCCGCCAGCGGCTGGCTGAGGTGGCATTGGCGTATGCCAAGGCA
GGATGTCAGGTGGTAGCCCCGTCGGACATGATGGATGGACGCGTGGAAGCCATCAAAGAG
GCCCTGATGGCACATGGACTTGGCAACAGGGTATCGGTGATGAGCTACAGTGCCAAATTT
GCTTCCTGTTTCTATGGCCCTTTCCGGGATGCAGCTAAGTCAAGCCCAGCTTTTGGGGAC
CGCCGCTGCTACCAGCTGCCCCCTGGAGCACGAGGCCTGGCTCTCCGAGCTGTGGACCGG
GATGTACGGGAAGGAGCTGACATGCTCATGGTGAAGCCGGGAATGCCCTACCTGGACATC
GTGCGGGAGGTAAAGGACAAGCACCCTGACCTCCCTCTCGCCGTGTACCACGTCTCTGGA
GAGTTTGCCATGCTGTGGCATGGAGCCCAGGCCGGGGCATTTGATCTCAAGGCTGCCGTA
CTGGAGGCCATGACTGCCTTCCGCAGAGCAGGTGCTGACATCATCATCACCTACTACACA
CCGCAGCTGCTGCAGTGGCTGAAGGAGGAATGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID ALAD Link Image
Target 1 GenAtlas ID ALAD Link Image
Target 1 HGNC ID HGNC:395 Link Image
Target 1 Chromosome Location 9
Target 1 Locus 9q33.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. 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 Link Image]
  2. Akagi R, Shimizu R, Furuyama K, Doss MO, Sassa S: Novel molecular defects of the delta-aminolevulinate dehydratase gene in a patient with inherited acute hepatic porphyria. Hepatology. 2000 Mar;31(3):704-8. [PubMed Link Image]
  3. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [PubMed Link Image]
  4. Ishida N, Fujita H, Fukuda Y, Noguchi T, Doss M, Kappas A, Sassa S: Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria. J Clin Invest. 1992 May;89(5):1431-7. [PubMed Link Image]
  5. Astrin KH, Kaya AH, Wetmur JG, Desnick RJ: RsaI polymorphism in the human delta-aminolevulinate dehydratase gene at 9q34. Nucleic Acids Res. 1991 Aug 11;19(15):4307. [PubMed Link Image]
  6. Wetmur JG, Kaya AH, Plewinska M, Desnick RJ: Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Genet. 1991 Oct;49(4):757-63. [PubMed Link Image]
  7. Plewinska M, Thunell S, Holmberg L, Wetmur JG, Desnick RJ: delta-Aminolevulinate dehydratase deficient porphyria: identification of the molecular lesions in a severely affected homozygote. Am J Hum Genet. 1991 Jul;49(1):167-74. [PubMed Link Image]
  8. Gibbs PN, Jordan PM: Identification of lysine at the active site of human 5-aminolaevulinate dehydratase. Biochem J. 1986 Jun 1;236(2):447-51. [PubMed Link Image]
  9. Wetmur JG, Bishop DF, Cantelmo C, Desnick RJ: Human delta-aminolevulinate dehydratase: nucleotide sequence of a full-length cDNA clone. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7703-7. [PubMed Link Image]
Target 1 Drug References
  1. Sakai T: Biomarkers of lead exposure. Ind Health. 2000 Apr;38(2):127-42. [PubMed Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]
  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 Link Image]

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