Aminolevulinic acid
Identification
- Summary
Aminolevulinic acid is a porphyrin precursor used to treat actinic keratosis of the face, scalp, and upper extremities, as well as to visualize a glioma.
- Brand Names
- Ameluz, Gliolan, Levulan
- Generic Name
- Aminolevulinic acid
- DrugBank Accession Number
- DB00855
- Background
A compound produced from succinyl-CoA and glycine as an intermediate in heme synthesis. It is used as a photochemotherapy for actinic keratosis. [PubChem]
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Aminolevulinic acid (DB00855)
- Weight
- Average: 131.1299
Monoisotopic: 131.058243159 - Chemical Formula
- C5H9NO3
- Synonyms
- 5-ALA
- 5-Aminolevulinic acid
- ácido 5-aminolevulínico
- Aminolevulinic acid
- dALA
- δ-ALA
- δ-aminolevulinic acid
- External IDs
- EINECS 226-679-5
- NSC 18509
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.
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- Contraindications & Blackbox Warnings
Contraindications & Blackbox WarningsWith our commercial data, access important information on dangerous risks, contraindications, and adverse effects.Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects- 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).
Target Actions Organism ADelta-aminolevulinic acid dehydratase inducerHumans - 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
- Adverse Effects
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Solution overdose have not been reported.
- Pathways
Pathway Category Glycine and Serine Metabolism Metabolic Porphyrin Metabolism Metabolic Non-Ketotic Hyperglycinemia Disease Sarcosinemia Disease Acute Intermittent Porphyria Disease Porphyria Variegata (PV) Disease Dihydropyrimidine Dehydrogenase Deficiency (DHPD) Disease Dimethylglycine Dehydrogenase Deficiency Disease Hereditary Coproporphyria (HCP) Disease Congenital Erythropoietic Porphyria (CEP) or Gunther Disease Disease Dimethylglycine Dehydrogenase Deficiency Disease Hyperglycinemia, Non-Ketotic Disease 3-Phosphoglycerate Dehydrogenase Deficiency Disease - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareDarbepoetin alfa The risk or severity of Thrombosis can be increased when Darbepoetin alfa is combined with Aminolevulinic acid. Erythropoietin The risk or severity of Thrombosis can be increased when Erythropoietin is combined with Aminolevulinic acid. Methoxy polyethylene glycol-epoetin beta The risk or severity of Thrombosis can be increased when Methoxy polyethylene glycol-epoetin beta is combined with Aminolevulinic acid. Peginesatide The risk or severity of Thrombosis can be increased when Peginesatide is combined with Aminolevulinic acid. Porfimer sodium Aminolevulinic acid may increase the photosensitizing activities of Porfimer sodium. Tretinoin The risk or severity of adverse effects can be increased when Tretinoin is combined with Aminolevulinic acid. Verteporfin Aminolevulinic acid may increase the photosensitizing activities of Verteporfin. 
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- No interactions found.
Products
Comprehensive & structured drug product infoFrom application numbers to product codes, connect different identifiers through our commercial datasets.Easily connect various identifiers back to our datasets- Product Ingredients
Ingredient UNII CAS InChI Key Aminolevulinic acid hydrochloride V35KBM8JGR 5451-09-2 ZLHFONARZHCSET-UHFFFAOYSA-N - International/Other Brands
- Levulan (DUSA Pharmaceuticals, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Ameluz Gel Cutaneous Biofrontera Bioscience Gmb H 2016-09-08 Not applicable EU 
Ameluz Gel 100 mg/1g Topical Biofrontera Inc. 2016-08-26 Not applicable US 
Gleolan Powder, for solution 1500 mg/1 Oral Nx Development Corp 2018-03-14 Not applicable US Gleolan Powder, for solution 1.5 g Oral Medexus Inc 2021-02-22 Not applicable Canada 
Gliolan Powder, for solution Oral Medac 2016-09-07 Not applicable EU Gliolan Powder, for solution Oral Medac 2016-09-07 Not applicable EU Gliolan Powder, for solution Oral Medac 2016-09-07 Not applicable EU Levulan Kerastick Powder, for solution 20 % Topical Dusa Pharmaceuticals Inc 2004-06-03 Not applicable Canada Levulan Kerastick 354 mg/1.5mL Topical DUSA Pharmaceuticals, Inc. 2000-09-04 Not applicable US
Categories
- ATC Codes
- L01XD04 — Aminolevulinic acid
- Drug Categories
- Amino Acids
- Amino Acids, Peptides, and Proteins
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Dermatologicals
- Enkephalins
- Keto Acids
- Levulinic Acids
- Misc. Skin and Mucous Membrane Agents
- Nerve Tissue Proteins
- Neuropeptides
- Opioid Peptides
- Peptides
- Photosensitizing Agents
- Photosensitizing agents used for phototherapy
- Porphyrin Precursor
- Proteins
- Radiation-Sensitizing Agents
- Roentgenography
- Sensitizers Used in Photodynamic/radiation Therapy
- Chemical TaxonomyProvided by Classyfire
- Description
- This 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.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Delta amino acids and derivatives
- Alternative Parents
- Gamma-keto acids and derivatives / Short-chain keto acids and derivatives / Alpha-amino ketones / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
- Substituents
- Aliphatic acyclic compound / Alpha-aminoketone / Amine / Amino acid / Carbonyl group / Carboxylic acid / Delta amino acid or derivatives / Gamma-keto acid / Hydrocarbon derivative / Keto acid
- Molecular Framework
- Aliphatic acyclic compounds
- External Descriptors
- delta-amino acid, 4-oxo monocarboxylic acid (CHEBI:17549) / Amino fatty acids (LMFA01100055)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 88755TAZ87
- CAS number
- 106-60-5
- InChI Key
- 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
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
- 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]
- 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
- Human Metabolome Database
- HMDB0001149
- KEGG Compound
- C00430
- PubChem Compound
- 137
- PubChem Substance
- 46506856
- ChemSpider
- 134
- BindingDB
- 50240386
- 155002
- ChEBI
- 17549
- ChEMBL
- CHEMBL601
- ZINC
- ZINC000003782550
- Therapeutic Targets Database
- DAP000314
- PharmGKB
- PA10015
- PDBe Ligand
- FVT
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Aminolevulinic_acid
- AHFS Codes
- 84:92.00 — Misc. Skin and Mucous Membrane Agents
- 36:68.00 — Roentgenography
- PDB Entries
- 6h7u / 6hzp
- FDA label
- Download (195 KB)
- MSDS
- Download (72.5 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Actinic Cheilitis 1 4 Completed Treatment Actinic Keratosis (AK) 2 4 Completed Treatment Actinic Keratosis (AK) / Natural Daylight Photodynamic Therapy 1 4 Completed Treatment Hutchinson's Melanotic Freckle 1 4 Completed Treatment Multiple Actinic Keratoses 1 4 Completed Treatment Normal Skin 1 4 Recruiting Prevention Actinic Keratosis (AK) 1 4 Recruiting Treatment Actinic Keratosis (AK) / Photodamaged Skin 1 4 Terminated Treatment Actinic Keratosis (AK) 1 4 Unknown Status Treatment Acne Rosacea / Papulopustular Rosacea (PPR) 1
Pharmacoeconomics
- Manufacturers
- Dusa pharmaceuticals inc
- Packagers
- Dusa Pharmaceuticals
- Dosage Forms
Form Route Strength Patch Topical Plaster Gel Cutaneous Gel Topical 100 mg/1g Powder, for solution Oral 1.5 g Powder, for solution Oral 1500 mg/1 Powder, for solution Oral Powder, for solution Topical 20 % - Prices
Unit description Cost Unit Levulan kerastick 170.25USD each DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5422093 No 1995-06-06 2009-07-28 US US5954703 No 1999-09-21 2017-10-31 US US6709446 No 2004-03-23 2018-05-01 US US7723910 No 2010-05-25 2019-06-17 US US8216289 No 2012-07-10 2018-05-01 US US8758418 No 2014-06-24 2018-05-01 US US6559183 No 2003-05-06 2019-11-12 US US10357567 No 2019-07-23 2038-01-12 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 156-158 °C Not Available water solubility Very soluble Not Available logP -1.5 Not Available - Predicted Properties
Property Value Source Water Solubility 173.0 mg/mL ALOGPS logP -2.8 ALOGPS logP -3.3 ChemAxon logS 0.12 ALOGPS pKa (Strongest Acidic) 4.05 ChemAxon pKa (Strongest Basic) 7.84 ChemAxon Physiological Charge 0 ChemAxon Hydrogen Acceptor Count 4 ChemAxon Hydrogen Donor Count 2 ChemAxon Polar Surface Area 80.39 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 30.45 m3·mol-1 ChemAxon Polarizability 12.55 Å3 ChemAxon Number of Rings 0 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter No ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9162 Blood Brain Barrier + 0.7482 Caco-2 permeable - 0.7802 P-glycoprotein substrate Non-substrate 0.6653 P-glycoprotein inhibitor I Non-inhibitor 0.9515 P-glycoprotein inhibitor II Non-inhibitor 0.7522 Renal organic cation transporter Non-inhibitor 0.9017 CYP450 2C9 substrate Non-substrate 0.8819 CYP450 2D6 substrate Non-substrate 0.8314 CYP450 3A4 substrate Non-substrate 0.7939 CYP450 1A2 substrate Non-inhibitor 0.9219 CYP450 2C9 inhibitor Non-inhibitor 0.9561 CYP450 2D6 inhibitor Non-inhibitor 0.9608 CYP450 2C19 inhibitor Non-inhibitor 0.9406 CYP450 3A4 inhibitor Non-inhibitor 0.9187 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9784 Ames test Non AMES toxic 0.8884 Carcinogenicity Non-carcinogens 0.8377 Biodegradation Ready biodegradable 0.9445 Rat acute toxicity 1.1726 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9186 hERG inhibition (predictor II) Non-inhibitor 0.8944
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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- Kind
- Protein
- Organism
- Humans
- 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
- Uniprot Name
- Delta-aminolevulinic acid dehydratase
- Molecular Weight
- 36294.485 Da
References
- Sakai T: Biomarkers of lead exposure. Ind Health. 2000 Apr;38(2):127-42. [PubMed:10812836]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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
- Humans
- 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
- Uniprot Name
- Solute carrier family 15 member 1
- Molecular Weight
- 78805.265 Da
References
- 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]
- 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]
- 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
- Humans
- 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
- Uniprot Name
- Solute carrier family 15 member 2
- Molecular Weight
- 81782.77 Da
References
- 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]
- 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]
Drug created on June 13, 2005 13:24 / Updated on May 06, 2021 06:19