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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
5-ALA
5-Amino-4-oxopentanoate
5-Amino-4-oxovaleric acid
5-Aminolevulinate
5-Aminolevulinic acid
ALA
ALA-PDT
Aminolevulinate
Aminolevulinic acid
DALA
delta-ALA
delta-Aminolevulinic acid
External Identifiers
  • EINECS 226-679-5
  • NSC 18509
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Levulan KerastickkitDUSA Pharmaceuticals, Inc.2000-09-04Not applicableUs
Levulan Kerastickpowder for solution20 %topicalDusa Pharmaceuticals Inc2004-06-03Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
Gliolanmedac GmbH
LevulanDUSA Pharmaceuticals, Inc.
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Aminolevulinic acid hydrochloride
ThumbNot applicableDBSALT000934
Categories
UNII88755TAZ87
CAS number106-60-5
WeightAverage: 131.1299
Monoisotopic: 131.058243159
Chemical FormulaC5H9NO3
InChI KeyInChIKey=ZGXJTSGNIOSYLO-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).
Related Articles
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
Hyperglycinemia, non-ketoticDiseaseSMP00485
Non Ketotic HyperglycinemiaDiseaseSMP00223
Hereditary Coproporphyria (HCP)DiseaseSMP00342
Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00484
Congenital Erythropoietic Porphyria (CEP) or Gunther DiseaseDiseaseSMP00345
Porphyria Variegata (PV)DiseaseSMP00346
3-Phosphoglycerate dehydrogenase deficiencyDiseaseSMP00721
Glycine and Serine MetabolismMetabolicSMP00004
Porphyrin MetabolismMetabolicSMP00024
Dihydropyrimidine Dehydrogenase Deficiency (DHPD)DiseaseSMP00179
Dimethylglycine Dehydrogenase DeficiencyDiseaseSMP00242
SarcosinemiaDiseaseSMP00244
Acute Intermittent PorphyriaDiseaseSMP00344
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 inhibitorNon-inhibitor0.9561
CYP450 2D6 inhibitorNon-inhibitor0.9608
CYP450 2C19 inhibitorNon-inhibitor0.9406
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Dusa pharmaceuticals inc
Packagers
Dosage forms
FormRouteStrength
Kit
Powder for solutiontopical20 %
Prices
Unit descriptionCostUnit
Levulan kerastick170.25USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5422093 No1992-07-282009-07-28Us
US5954703 No1997-10-312017-10-31Us
US6709446 No1998-05-012018-05-01Us
US7723910 No1999-06-172019-06-17Us
US8216289 No1998-05-012018-05-01Us
US8758418 No1998-05-012018-05-01Us
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
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-0fki-2910000000-12bd38ce6e25c61b8e60View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS)splash10-00dr-4900000000-c11a861a1638dd2c20d8View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-00dr-2911000000-d5b5567862328f5a46cdView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-00dr-3900000000-538e027ec9932b3f56a5View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS; 1 MEOX)splash10-00di-9500000000-c0d571fa1aa74cf69ea6View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (3 TMS; 1 MEOX)splash10-00di-9600000000-d0a9f31de64870117dfeView in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 3 TMS)splash10-00di-1911000000-117a44ade2fd70812e5cView in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 MEOX; 3 TMS)splash10-00dr-2900000000-635a7d4012b9ef5150f9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-0udi-5900000000-cf9a0266243b1a1d0f73View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-000i-9000000000-995eb11961b16f254be2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0fb9-9000000000-64b1ef51cceb8d346f52View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Positivesplash10-01q9-1900000000-a5686c059e357bc14e96View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Positivesplash10-000i-9300000000-8e219c18bb0fd0837d82View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Positivesplash10-0avr-9000000000-b0d0d9b25a36e5c49f2aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Positivesplash10-0a4i-9000000000-96cc61ad07db2c38c952View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Positivesplash10-0a4i-9000000000-7b8165e702ac7e6d5f34View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Positivesplash10-01p9-8900000000-0b739a89ed524e47e3a2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-001i-0900000000-1ffb96adb6268888f722View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-4900000000-1669ed2d77c2a1921a2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0292-9300000000-c07de16859b85d8fb54cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-067j-9000000000-316eb66f80f8b40f4ae2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-4900000000-1669ed2d77c2a1921a2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0292-9300000000-c07de16859b85d8fb54cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-067j-9000000000-316eb66f80f8b40f4ae2View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-e2f3aecb5b3f533e4905View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bu0-9600000000-fc4f9eaeca47b90745aeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9000000000-304beef010b4b4fdbb53View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2900000000-e2f3aecb5b3f533e4905View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bu0-9600000000-fc4f9eaeca47b90745aeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-9000000000-304beef010b4b4fdbb53View in MoNA
1D NMR1H NMR SpectrumNot Available
2D NMR[1H,13C] 2D NMR SpectrumNot Available
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 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:16648043 ]
  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:9612195 ]
External Links
ATC CodesL01XD04
AHFS Codes
  • 84:92.00
PDB EntriesNot Available
FDA labelDownload (195 KB)
MSDSDownload (72.5 KB)
Interactions
Drug Interactions
Drug
PorfimerAminolevulinic acid may increase the photosensitizing activities of Porfimer.
VerteporfinAminolevulinic acid may increase the photosensitizing activities of Verteporfin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inducer
General Function:
Zinc ion binding
Specific Function:
Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Gene Name:
ALAD
Uniprot ID:
P13716
Molecular Weight:
36294.485 Da
References
  1. Sakai T: Biomarkers of lead exposure. Ind Health. 2000 Apr;38(2):127-42. [PubMed:10812836 ]
  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:10879826 ]
  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:11906825 ]
  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:12079382 ]
  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:12107644 ]
  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:10519994 ]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
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.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular Weight:
78805.265 Da
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:11007306 ]
  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:9637710 ]
  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:16627568 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. 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:9637710 ]
  2. 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:11007306 ]
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Drug created on June 13, 2005 07:24 / Updated on July 26, 2016 01:51