Methyl aminolevulinate

Identification

Name
Methyl aminolevulinate
Accession Number
DB00992  (APRD01105)
Type
Small Molecule
Groups
Approved
Description

Methyl aminolevulinate is a prodrug that is metabolised to Protoporphyrin IX (a photosensitizer) used in photodynamic therapy.

Structure
Thumb
Synonyms
  • 5-Aminolevulinic acid methyl ester
  • Aminolevulinic acid methyl ester
  • Methyl aminolevulinate
  • Methyl delta-aminolevulinate
External IDs
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Methyl aminolevulinate hydrochloride7S73606O1A 79416-27-6UJYSYPVQHFNBML-UHFFFAOYSA-N
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MetvixCream168 mgTopicalGalderma2009-06-16Not applicableCanada
Approved Generic Prescription Products
Not Available
Approved Over the Counter Products
Not Available
Unapproved/Other Products
Not Available
International/Other Brands
Not Available
Brand mixtures
Not Available
Categories
UNII
585NM85KYM
CAS number
33320-16-0
Weight
Average: 145.1564
Monoisotopic: 145.073893223
Chemical Formula
C6H11NO3
InChI Key
YUUAYBAIHCDHHD-UHFFFAOYSA-N
InChI
InChI=1S/C6H11NO3/c1-10-6(9)3-2-5(8)4-7/h2-4,7H2,1H3
IUPAC Name
methyl 5-amino-4-oxopentanoate
SMILES
COC(=O)CCC(=O)CN

Pharmacology

Indication

For topical use, in combination with 570 to 670 nm wavelength red light illumination, in the treatment of non-hyperkeratotic actinic keratoses of the face and scalp in immunocompetent patients when used in conjunction with lesion preparation (debridement using a sharp dermal curette).

Structured Indications
Pharmacodynamics

After topical application of methyl aminolevulinate, porphyrins will accumulate intracellularly in the treated skin lesions. The intracellular porphyrins (including PpIX) are photoactive, fluorescing compounds and, upon light activation in the presence of oxygen, singlet oxygen is formed which causes damage to cellular compartments, in particular the mitochondria. Light activation of accumulated porphyrins leads to a photochemical reaction and thereby phototoxicity to the light-exposed target cells.

Mechanism of action

Photosensitization following application of methyl aminolevulinate cream occurs through the metabolic conversion of methyl aminolevulinate (prodrug) to photoactive porphyrins (PAP), which accumulates in the skin lesions to which the cream has been applied. When exposed to light of appropriate wavelength and energy, the accumulated photoactive porphyrins produce a photodynamic reaction, resulting in a cytotoxic process dependent upon the simultaneous presence of oxygen. The absorption of light results in an excited state of porphyrin molecules, and subsequent spin transfer from photoactive porphyrins to molecular oxygen generates singlet oxygen, which can further react to form superoxide and hydroxyl radicals.

TargetActionsOrganism
UHigh affinity immunoglobulin gamma Fc receptor I
antibody
Human
Absorption

In vitro, after 24 hours the mean cumulative absorption through human skin was 0.26% of the administered dose.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

The severity of local phototoxic reactions such as erythema, pain and burning sensation may increase in case of prolonged application time or very high light intensity.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Methyl aminolevulinate.Approved
BevacizumabBevacizumab may increase the cardiotoxic activities of Methyl aminolevulinate.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Methyl aminolevulinate.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Methyl aminolevulinate.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Methyl aminolevulinate.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Methyl aminolevulinate.Approved
DigoxinDigoxin may decrease the cardiotoxic activities of Methyl aminolevulinate.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Methyl aminolevulinate.Approved, Investigational
OleandrinAnvirzel may decrease the cardiotoxic activities of Methyl aminolevulinate.Experimental
OuabainOuabain may decrease the cardiotoxic activities of Methyl aminolevulinate.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Methyl aminolevulinate.Approved, Vet Approved
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Methyl aminolevulinate.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference
Not Available
General References
  1. Smits T, Moor AC: New aspects in photodynamic therapy of actinic keratoses. J Photochem Photobiol B. 2009 Sep 4;96(3):159-69. doi: 10.1016/j.jphotobiol.2009.06.003. Epub 2009 Jun 13. [PubMed:19592269 ]
External Links
Human Metabolome Database
HMDB15127
PubChem Compound
157922
PubChem Substance
46507004
ChemSpider
138950
ChEBI
724125
ChEMBL
CHEMBL1096562
Therapeutic Targets Database
DAP001024
PharmGKB
PA164784028
Drugs.com
Drugs.com Drug Page
Wikipedia
Methyl_aminolevulinate
ATC Codes
L01XD03 — Methyl aminolevulinate
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Download (597 KB)
MSDS
Not Available

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentBasal Cell Carcinoma of the Skin / Pain / Recurrent Skin Cancer1
1, 2CompletedTreatmentActinic Keratosis (AK)1
1, 2CompletedTreatmentCervical Dysplasia1
1, 2RecruitingTreatmentBasal Cell Carcinoma (BCC) / Neoplasms, Basal Cell / Photochemotherapy / Photosensitizing Agents1
2CompletedTreatmentFacial Photodamage1
3Active Not RecruitingTreatmentBasal Cell Carcinoma (BCC)1
3CompletedTreatmentActinic Keratosis (AK)3
3CompletedTreatmentSkin Aging1
3RecruitingTreatmentActinic Keratosis (AK)1
4Active Not RecruitingTreatmentActinic Keratosis (AK) / Natural Daylight Photodynamic Therapy1
4CompletedTreatmentActinic Keratoses (gr I-III) / Multiple Actinic Keratoses1
Not AvailableNo Longer AvailableNot AvailableBasal Cell Carcinoma (BCC) / Field Actinic Keratoses / Squamous Cell Carcinoma (SCC)1
Not AvailableRecruitingTreatmentActinic Keratosis (AK)1
Not AvailableRecruitingTreatmentSquamous Cell Carcinoma (SCC) / Superficial Basal Cell Carcinoma1

Pharmacoeconomics

Manufacturers
  • Galderma laboratories lp
Packagers
Dosage forms
FormRouteStrength
CreamTopical168 mg
Prices
Unit descriptionCostUnit
Metvixia 16.8% cream82.2USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2215069 No2006-09-122016-03-08Canada
US6034267 No1996-03-082016-03-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityFreely solubleNot Available
logP-1.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility220.0 mg/mLALOGPS
logP-1.3ALOGPS
logP-0.85ChemAxon
logS0.18ALOGPS
pKa (Strongest Acidic)16.12ChemAxon
pKa (Strongest Basic)7.83ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area69.39 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity35.22 m3·mol-1ChemAxon
Polarizability14.55 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9652
Blood Brain Barrier+0.9677
Caco-2 permeable-0.5715
P-glycoprotein substrateNon-substrate0.6238
P-glycoprotein inhibitor INon-inhibitor0.806
P-glycoprotein inhibitor IINon-inhibitor0.7456
Renal organic cation transporterNon-inhibitor0.7855
CYP450 2C9 substrateNon-substrate0.8561
CYP450 2D6 substrateNon-substrate0.7888
CYP450 3A4 substrateNon-substrate0.6617
CYP450 1A2 substrateNon-inhibitor0.5854
CYP450 2C9 inhibitorNon-inhibitor0.9022
CYP450 2D6 inhibitorNon-inhibitor0.9309
CYP450 2C19 inhibitorNon-inhibitor0.8932
CYP450 3A4 inhibitorNon-inhibitor0.8724
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8936
Ames testNon AMES toxic0.8519
CarcinogenicityNon-carcinogens0.8042
BiodegradationReady biodegradable0.899
Rat acute toxicity1.7684 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8837
hERG inhibition (predictor II)Non-inhibitor0.8402
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted LC-MS/MS Spectrum - 10V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, PositivePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 10V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 20V, NegativePredicted LC-MS/MSNot Available
Predicted LC-MS/MS Spectrum - 40V, NegativePredicted LC-MS/MSNot Available

Taxonomy

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 / Fatty acid methyl esters / Methyl esters / Alpha-amino ketones / Monocarboxylic acids and derivatives / Organopnictogen compounds / Organic oxides / Monoalkylamines / Hydrocarbon derivatives
Substituents
Delta amino acid or derivatives / Gamma-keto acid / Fatty acid ester / Fatty acid methyl ester / Keto acid / Fatty acyl / Alpha-aminoketone / Methyl ester / Carboxylic acid ester / Ketone
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
delta-amino acid ester (CHEBI:724125 )

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antibody
General Function
Receptor signaling protein activity
Specific Function
High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.
Gene Name
FCGR1A
Uniprot ID
P12314
Uniprot Name
High affinity immunoglobulin gamma Fc receptor I
Molecular Weight
42631.525 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
Drug created on June 13, 2005 07:24 / Updated on September 01, 2017 10:34