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Details

Stereochemistry ACHIRAL
Molecular Formula C5H9NO3
Molecular Weight 131.1299
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of AMINOLEVULINIC ACID

SMILES

NCC(=O)CCC(O)=O

InChI

InChIKey=ZGXJTSGNIOSYLO-UHFFFAOYSA-N
InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)

HIDE SMILES / InChI

Molecular Formula C5H9NO3
Molecular Weight 131.1299
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Aminolevulinic Acid is the first compound in the porphyrin synthesis pathway. 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. Marketed under the brand name LEVULAN KERASTICK for Topical Solution plus blue light illumination using the BLU-U Blue Light Photodynamic Therapy Illuminator, it is indicated for the treatment of minimally to moderately thick actinic keratoses (Grade 1 or 2, see table 2 for definition) of the face or scalp. Aminolevulinic acid is also being studied in the treatment of other conditions and types of cancer. An orally-administered in vivo diagnostic agent, Aminolevulinic acid, is used in photodynamic diagnosis (PDD) whose aim is to help doctors visualize the tumor tissue during surgical resection of malignant glioma, it is already sold in over 20 European countries including Germany and the U.K. 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).

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
LEVULAN KERASTICK
Diagnostic
Gliolan
Primary
ALA

Cmax

ValueDoseCo-administeredAnalytePopulation
15.44 μg/mL
100 mg single, intravenous
AMINOLEVULINIC ACID plasma
Homo sapiens
4.65 μg/mL
100 mg single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
274.7 μg/L
0.2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
1862.6 μg/L
2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
8239.1 μg/L
20 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
13.7 μg × h/mL
100 mg single, intravenous
AMINOLEVULINIC ACID plasma
Homo sapiens
7.4 μg × h/mL
100 mg single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
424.2 μg × h/L
0.2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
2901.3 μg × h/L
2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
27143.5 μg × h/L
20 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
50.1 min
100 mg single, intravenous
AMINOLEVULINIC ACID plasma
Homo sapiens
44.4 min
100 mg single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
0.75 h
0.2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
0.84 h
2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
1.94 h
20 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
88%
0.2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
88%
2 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens
88%
20 mg/kg bw single, oral
AMINOLEVULINIC ACID plasma
Homo sapiens

Doses

AEs

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
LEVULAN KERASTICK for Topical Solution 20% (aminolevulinic acid HCl) is intended for direct application to individual lesions diagnosed as actinic keratoses and not to perilesional skin. This product is not intended for application by patients or unqualified medical personnel. Application should involve either scalp or face lesions, but not both simultaneously. The recommended treatment frequency is: one application of the LEVULAN KERASTICK Topical Solution and one dose of illumination per treatment site per 8­ week treatment session. Each individual LEVULAN KERASTICK should be used for only one patient. Photodynamic therapy for actinic keratoses with LEVULAN KERASTICK for Topical Solution is a two stage process involving a) application of the product to the target lesions with LEVULAN KERASTICK Topical Solution, followed 14 to 18 hours later by b) illumination with blue light using the BLU-U Blue Light Photodynamic Therapy Illuminator. The second visit, for illumination, must take place in the 14-18 hour window following application.
Route of Administration: Topical
In Vitro Use Guide
Aminolevulinic acid (10 ug/ml) mediated sonosensitization of rat RG2 glioma cells in vitro. ALA-mediated SDT evokes cytotoxic effects of low intensity US on rat RG2 glioma cells in vitro.
Substance Class Chemical
Record UNII
88755TAZ87
Record Status Validated (UNII)
Record Version