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Identification
NameAminolevulinic acid
Accession NumberDB00855  (APRD00793, DB05277)
TypeSmall Molecule
GroupsApproved
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
Synonyms
SynonymLanguageCode
5-ALANot AvailableNot Available
5-Amino-4-oxopentanoateNot AvailableNot Available
5-Amino-4-oxovaleric acidNot AvailableNot Available
5-AminolevulinateNot AvailableNot Available
5-Aminolevulinic acidNot AvailableIS
ALANot AvailableIS
ALA-PDTNot AvailableIS
AminolevulinateNot AvailableNot Available
Aminolevulinic acidNot AvailableNot Available
DALANot AvailableNot Available
delta-ALANot AvailableNot Available
delta-Aminolevulinic acidNot AvailableNot Available
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levulan KerastickkitDUSA Pharmaceuticals, Inc.2000-09-04Not AvailableUs 0a2ef1ad1c84951dc1392a8bbe1f3cb241c91ed59e44ad8268635315440d978c
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
Gliolanmedac GmbH
LevulanDUSA Pharmaceuticals, Inc.
Brand mixturesNot Available
Salts
Name/CASStructureProperties
5-Aminolevulinate hydrochloride
ThumbNot applicableDBSALT000934
Categories
CAS number106-60-5
WeightAverage: 131.1299
Monoisotopic: 131.058243159
Chemical FormulaC5H9NO3
InChI KeyZGXJTSGNIOSYLO-UHFFFAOYSA-N
InChI
InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)
IUPAC Name
5-amino-4-oxopentanoic acid
SMILES
NCC(=O)CCC(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as delta amino acids and derivatives. These are compounds containing a carboxylic acid group and an amino group at the C5 carbon atom.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentDelta amino acids and derivatives
Alternative Parents
Substituents
  • Delta amino acid or derivatives
  • Gamma-keto acid
  • Short-chain keto acid
  • Keto acid
  • Alpha-aminoketone
  • Ketone
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationAminolevulinic 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.
PharmacodynamicsThe 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 actionAccording 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).
AbsorptionOral bioavailability is 50-60%.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Following topical administration, synthesis into protoporphyrin IX takes place in situ in the skin.

Route of eliminationNot Available
Half lifeMean half-life is 0.70 ± 0.18 h after the oral dose and 0.83 ± 0.05 h after the intravenous dose.
ClearanceNot Available
ToxicitySolution overdose have not been reported.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Congenital Erythropoietic Porphyria (CEP) or Gunther DiseaseDiseaseSMP00345
Porphyria Variegata (PV)DiseaseSMP00346
Porphyrin MetabolismMetabolicSMP00024
Hereditary Coproporphyria (HCP)DiseaseSMP00342
Acute Intermittent PorphyriaDiseaseSMP00344
Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00242
Glycine and Serine MetabolismMetabolicSMP00004
SarcosinemiaDiseaseSMP00244
Hyperglycinemia, non-ketoticDiseaseSMP00485
Non Ketotic HyperglycinemiaDiseaseSMP00223
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)DiseaseSMP00179
Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00484
3-Phosphoglycerate dehydrogenase deficiencyDiseaseSMP00721
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9162
Blood Brain Barrier+0.7482
Caco-2 permeable-0.7802
P-glycoprotein substrateNon-substrate0.6653
P-glycoprotein inhibitor INon-inhibitor0.9515
P-glycoprotein inhibitor IINon-inhibitor0.7522
Renal organic cation transporterNon-inhibitor0.9017
CYP450 2C9 substrateNon-substrate0.8819
CYP450 2D6 substrateNon-substrate0.8314
CYP450 3A4 substrateNon-substrate0.7939
CYP450 1A2 substrateNon-inhibitor0.9219
CYP450 2C9 substrateNon-inhibitor0.9561
CYP450 2D6 substrateNon-inhibitor0.9608
CYP450 2C19 substrateNon-inhibitor0.9406
CYP450 3A4 substrateNon-inhibitor0.9187
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9784
Ames testNon AMES toxic0.8884
CarcinogenicityNon-carcinogens0.8377
BiodegradationReady biodegradable0.9445
Rat acute toxicity1.1726 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9186
hERG inhibition (predictor II)Non-inhibitor0.8944
Pharmacoeconomics
Manufacturers
  • Dusa pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Kit
Prices
Unit descriptionCostUnit
Levulan kerastick170.25USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States54220931992-07-282009-07-28
United States77239101999-06-172019-06-17
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point156-158 °CNot Available
water solubilityVery solubleNot Available
logP-1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility173.0 mg/mLALOGPS
logP-2.9ALOGPS
logP-3.3ChemAxon
logS0.12ALOGPS
pKa (Strongest Acidic)4.05ChemAxon
pKa (Strongest Basic)7.84ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area80.39 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity30.45 m3·mol-1ChemAxon
Polarizability12.55 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
References
Synthesis Reference

Takashi Ebata, Hiroshi Kawakami, Katsuya Matsumoto, Koshi Koseki, Hajime Matsushita, “Method of preparing an acid additional salt of delta-aminolevulinic acid.” U.S. Patent US5284973, issued July, 1974.

US5284973
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
ATC CodesL01XD04
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (195 KB)
MSDSDownload (72.5 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Delta-aminolevulinic acid dehydratase

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Delta-aminolevulinic acid dehydratase P13716 Details

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. Solute carrier family 15 member 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 1 P46059 Details

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. Doring F, Walter J, Will J, Focking M, Boll M, Amasheh S, Clauss W, Daniel H: Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998 Jun 15;101(12):2761-7. Pubmed
  3. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM: Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol. 2006 Jul 1;574(Pt 1):149-66. Epub 2006 Apr 20. Pubmed
  4. Doring F, Walter J, Will J, Focking M, Boll M, Amasheh S, Clauss W, Daniel H: Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998 Jun 15;101(12):2761-7. Pubmed
  5. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM: Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol. 2006 Jul 1;574(Pt 1):149-66. Epub 2006 Apr 20. Pubmed

2. Solute carrier family 15 member 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 15 member 2 Q16348 Details

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.
  2. Doring F, Walter J, Will J, Focking M, Boll M, Amasheh S, Clauss W, Daniel H: Delta-aminolevulinic acid transport by intestinal and renal peptide transporters and its physiological and clinical implications. J Clin Invest. 1998 Jun 15;101(12):2761-7. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12