106-60-5 Usage
Description
5-aminolevulinic acid is the simplest delta-amino acid in which the hydrogens at the gamma position are replaced by an oxo group. It is metabolised to protoporphyrin IX, a photoactive compound which accumulates in the skin. Used (in the form of the hydrochloride salt)in combination with blue light illumination for the treatment of minimally to moderately thick actinic keratosis of the face or scalp. It has a role as a photosensitizing agent, an antineoplastic agent, a dermatologic drug, a prodrug, a plant metabolite, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a delta-amino acid and a 4-oxo monocarboxylic acid. It derives from a 4-oxopentanoic acid. It is a conjugate base of a 5-ammoniolevulinic acid. It is a conjugate acid of a 5-aminolevulinate. It is a tautomer of a 5-ammoniolevulinate.
Originator
Levulan Kerastick,DUSA
Pharmaceuticals Inc.
Uses
5-Aminolevulinic acid (ALA), a nonprotein amino acid involved in tetrapyrrole synthesis, has been widely applied in agriculture, medicine, and food production.5-Aminolevulinic acid (5-ALA) is an intermediate in heme biosynthesis and is useful in cancer treatment. It is a non-protein amino acid. 5-ALA also has applications in the field of agriculture. It is being studied as an inducing reagent for protoporphyrin IX (PPIX) dependent fluorescence diagnosis of metastatic lymph nodes. 5-ALA is used for photodynamic therapy of diseases, such as Paget′s disease and HPV infection-associated cervical condylomata acuminata.Intermediate in heme biosynthesis.
Indications
Aminolevulinic acid (ALA HCl, Levulan Kerastick) is
indicated for the treatment of nonhyperkeratotic actinic
keratosis of the face and scalp. It has two components,
an alcohol solution vehicle and ALA HCl as a dry solid.
The two are mixed prior to application to the skin.
When applied to human skin, ALA is metabolized to
protoporphyrin, which accumulates and on exposure to
visible light produces a photodynamic reaction that
generates reactive oxygen species (ROS).The ROS produce
cytotoxic effects that may explain therapeutic efficacy.
Local burning and stinging of treated areas of skin
due to photosensitization can occur.
Manufacturing Process
1) Oxidation Step
2.27 g (10.0 mmol) of N-furfurylphthalimide was charged into a three-necked
glass flask equipped with an oxygen feed tube, a thermometer, and a reflux
condenser, and dissolved in 100 ml of anhydrous pyridine. After the addition
of 7.0 mg of Rose Bengal, oxygen gas was fed at a rate of 20 ml/min at 10°-
20°C under irradiation by light. A 27 W white fluorescent lamp was used as a
light source and the radiation was performed from the outside of the flask.
After 7 hours, the irradiation was terminated and the pyridine was evaporated
under reduced pressure to obtain 2.47 g of a light brown, semi-crystalline
product.
2) Reduction Step (Hydrogenation)
2.00 g of the semi-crystalline solid obtained in (1) was dissolved in 40 ml of
methanol and stirred at 50°C in a hydrogen atmosphere under atmospheric
pressure in the presence of 200 mg of 5% palladium-on-carbon catalyst.
After five hours, the reaction was terminated and the mixture was allowed to
cool to room temperature. The catalyst was removed by filtration and
methanol was evaporated to obtain 2.11 g of white crystals.
The crystals were identified to be 5-phthalimidolevulinic acid by NMR analysis.
The yield was 97%.
3) Hydrolysis Step
100 ml of 6 N hydrochloric acid was added to 2.11 g of the white crystals (2),
and the mixture was heated under reflux for 5 hours.
After evaporating the hydrochloric acid under reduced pressure, a brown solid
product was obtained and dissolved in ethanol. Acetone was added to the
solution and the crystals produced were collected by filtration to obtain 0.689
g of 5-aminolevulinic acid hydrochloride. The yield based on Nfurfurylphthalimide
was 51%.
NMR spectrum data conformed to 5-aminolevulinic acid hydrochloride
Therapeutic Function
Photosensitizer
Biological Activity
5-Aminolevulinic acid (5-ALA) is a precursor in the biosynthesis of porphyrins, including heme. The conversion of 5-ALA to protoporphyrins within tissues produces a photosensitive target that produces reactive oxygen species upon exposure to light.1 In this way, it is used in photodynamic therapy for a range of dermatological conditions, cancers, and other diseases. Also, oral administration of 5-ALA leads to the preferential accumulation of the fluorescent molecule protoporphyrin IX within certain types of cancer cells. This allows fluorescence-based identification of tumor tissue for accurate resection of diseased tissue.
Enzyme inhibitor
This key metabolic precursor (FW = 131.13 g/mol; CAS 106-60-5; pKa values = 4.05 and 8.90 at 25°C; Symbol: ALA), also known as daminolevulinic acid, is essential for the biosynthesis of metal ion-binding tetrapyrrole ring systems (porphyrins, chlorophylls, and cobalamins). In non-photosynthetic eukaryotes (animals, insects, fungi, protozoa, and alphaproteobacteria), d-aminolevulinic acid is produced by the enzyme ALA synthase, using glycine and succinyl CoA as substrates. In plants, algae, bacteria, and archaea, it is produced from glutamyl-tRNA and glutamate-1-semialdehyde. 5-Aminolevulinic acid inhibits (R)-3-amino-2- methylpropionate:pyruvate aminotransferase. ALA Phototherapy: Protoporphyrin IX, the immediate heme precursor is a highly effective tissue photosensitizer that is synthesized in four steps from 5- aminolevulinic acid. ALA synthesis is regulated via a feedback inhibition and gene repression mechanism linked to the concentration of free heme. In certain cell and tissue types, addition of exogenous ALA bypasses these regulation mechanisms, inducing uptake and synthesis of photosensitizing concentrations of Protoporphyrin IX, or PpIX. Topical application of ALA to certain malignant and non-malignant skin lesions, for example, can induce a clinically useful degree of lesion-specific photosensitization (e.g., superficial basal cell carcinomas show high response rate (~79%) after a single phototherapy treatment). ALA also induces localized tissue-specific photosensitization, when injected intradermally. In this sense, ALA and its methyl ester (methyl aminolevulinate, or MAL; trade name: Metvix?) are prodrugs that increase the amounts of the active drug (PpIX).
Check Digit Verification of cas no
The CAS Registry Mumber 106-60-5 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,0 and 6 respectively; the second part has 2 digits, 6 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 106-60:
(5*1)+(4*0)+(3*6)+(2*6)+(1*0)=35
35 % 10 = 5
So 106-60-5 is a valid CAS Registry Number.
InChI:InChI=1/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9)
106-60-5Relevant articles and documents
Functional asymmetry for the active sites of linked 5-aminolevulinate synthase and 8-amino-7-oxononanoate synthase
Turbeville, Tracy D.,Zhang, Junshun,Christopher Adams,Hunter, Gregory A.,Ferreira, Gloria C.
, p. 107 - 117 (2011)
5-Aminolevulinate synthase (ALAS) and 8-amino-7-oxononanoate synthase (AONS) are homodimeric members of the α-oxoamine synthase family of pyridoxal 5′-phosphate (PLP)-dependent enzymes. Previously, linking two ALAS subunits into a single polypeptide chain dimer yielded an enzyme (ALAS/ALAS) with a significantly greater turnover number than that of wild-type ALAS. To examine the contribution of each active site to the enzymatic activity of ALAS/ALAS, the catalytic lysine, which also covalently binds the PLP cofactor, was substituted with alanine in one of the active sites. Albeit the chemical rate for the pre-steady-state burst of ALA formation was identical in both active sites of ALAS/ALAS, the kcat values of the variants differed significantly (4.4 ± 0.2 vs. 21.6 ± 0.7 min-1) depending on which of the two active sites harbored the mutation. We propose that the functional asymmetry for the active sites of ALAS/ALAS stems from linking the enzyme subunits and the introduced intermolecular strain alters the protein conformational flexibility and rates of product release. Moreover, active site functional asymmetry extends to chimeric ALAS/AONS proteins, which while having a different oligomeric state, exhibit different rates of product release from the two ALAS and two AONS active sites due to the created intermolecular strain.
Handling heme: The mechanisms underlying the movement of heme within and between cells
Donegan, Rebecca K.,Moore, Courtney M.,Hanna, David A.,Reddi, Amit R.
, p. 88 - 100 (2019)
Heme is an essential cofactor and signaling molecule required for virtually all aerobic life. However, excess heme is cytotoxic. Therefore, heme must be safely transported and trafficked from the site of synthesis in the mitochondria or uptake at the cell surface, to hemoproteins in most subcellular compartments. While heme synthesis and degradation are relatively well characterized, little is known about how heme is trafficked and transported throughout the cell. Herein, we review eukaryotic heme transport, trafficking, and mobilization, with a focus on factors that regulate bioavailable heme. We also highlight the role of gasotransmitters and small molecules in heme mobilization and bioavailability, and heme trafficking at the host-pathogen interface.
Influence of precursors and inhibitor on the production of extracellular 5-aminolevulinic acid and biomass by rhodopseudomonas palustris kG31
Saikeur, Angkana,Choorit, Wanna,Prasertsan, Poonsuk,Kantachote, Duangporn,Sasaki, Ken
, p. 987 - 992 (2009)
5-Aminolevulinic acid (ALA) and the biomass of photosynthetic bacteria, Rhodopseudomonas palustris KG31, have very high potential for development and exploitation as bioherbicide and biofertilizer respectively. In this work, the effects of two precursors
Catalyst process-based aminolevulinic acid preparation method
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Paragraph 0038; 0039; 0040; 0041; 0042; 0043; 0044-0049, (2017/02/09)
The invention relates to the field of organic chemistry preparation, and discloses a catalyst process-based aminolevulinic acid preparation method. The method comprises the following steps: 1, synthesizing aminolaevulic acid (ALA): reacting a substance represented by molecular formula I with a substance represented by molecular formula II under the catalysis action of active carbon to generate the ALA; 2, filtering: cooling the product obtained in step 1, and filtering the cooled product; 3, forming salt and removing impurities: adding hydrochloric acid to a filtrate obtained in step 2, uniformly mixing hydrochloric acid and the filtrate, centrifuging the obtained solution, and carrying out evaporative concentration on the above obtained supernatant; and 4, purifying: adding a concentrate obtained in step 3 to acetone, fully mixing the concentrate and acetone, and drying the obtained mixture to obtain aminolevulinic acid. The preparation method has the advantages of simple technology, low cost, short production period, energy saving, environmental protection, and achieving of high yield and high purity of the target product.
