Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C5H9NO3.ClH |
| Molecular Weight | 167.591 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.NCC(=O)CCC(O)=O
InChI
InChIKey=ZLHFONARZHCSET-UHFFFAOYSA-N
InChI=1S/C5H9NO3.ClH/c6-3-4(7)1-2-5(8)9;/h1-3,6H2,(H,8,9);1H
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C5H9NO3 |
| Molecular Weight | 131.1299 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12493610 | https://www.ncbi.nlm.nih.gov/pubmed/9792218
Curator's Comment: There is low permeability of the undisrupted BBB in humans
Originator
Sources: http://www.mdpi.com/1420-3049/16/5/4140
Curator's Comment: The first report on excessive protoporphyrin accumulation and high photosensitivity after exogenous administration of ALA in humans was presented by Berlin et al. in 1956
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2311221 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | LEVULAN KERASTICK Approved UseThe LEVULAN KERASTICK for Topical Solution plus blue light illumination using the BLU-U Blue
Light Photodynamic Therapy Illuminator 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. Launch Date1999 |
|||
| Diagnostic | Gliolan Approved UseGliolan is indicated in adult patients for visualisation of malignant tissue during surgery for malignant
glioma (WHO grade III and IV). Launch Date2006 |
|||
| Primary | ALA Approved UseCondylomata Acuminata Launch Date2007 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
15.44 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
4.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
274.7 μg/L |
0.2 mg/kg bw single, oral dose: 0.2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1862.6 μg/L |
2 mg/kg bw single, oral dose: 2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
8239.1 μg/L |
20 mg/kg bw single, oral dose: 20 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
13.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
424.2 μg × h/L |
0.2 mg/kg bw single, oral dose: 0.2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
2901.3 μg × h/L |
2 mg/kg bw single, oral dose: 2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
27143.5 μg × h/L |
20 mg/kg bw single, oral dose: 20 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
50.1 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, intravenous dose: 100 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
44.4 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11961050/ |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
0.75 h |
0.2 mg/kg bw single, oral dose: 0.2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
0.84 h |
2 mg/kg bw single, oral dose: 2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
1.94 h |
20 mg/kg bw single, oral dose: 20 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
88% |
0.2 mg/kg bw single, oral dose: 0.2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
88% |
2 mg/kg bw single, oral dose: 2 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
88% |
20 mg/kg bw single, oral dose: 20 mg/kg bw route of administration: Oral experiment type: SINGLE co-administered: |
AMINOLEVULINIC ACID plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
20 mg/kg single, oral Recommended Dose: 20 mg/kg Route: oral Route: single Dose: 20 mg/kg Sources: |
unhealthy, 70.5 years (range: 53–84 years) Health Status: unhealthy Age Group: 70.5 years (range: 53–84 years) Sex: M+F Sources: |
Other AEs: Alanine aminotransferase increase, Hypotension... Other AEs: Alanine aminotransferase increase (grade 3, 6.6%) Sources: Hypotension (grade 3, 1.6%) Urticaria (grade 3, 1.6%) |
10 % 1 times / day multiple, topical Recommended Dose: 10 %, 1 times / day Route: topical Route: multiple Dose: 10 %, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
Disc. AE: Application site burning, Application site pain... AEs leading to discontinuation/dose reduction: Application site burning (1 patient) Sources: Application site pain (1 patient) |
100 mg single, intravenous Dose: 100 mg Route: intravenous Route: single Dose: 100 mg Sources: |
healthy |
|
100 mg single, oral |
healthy |
|
1328 mg single, intravesical Dose: 1328 mg Route: intravesical Route: single Dose: 1328 mg Sources: |
unhealthy |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypotension | grade 3, 1.6% | 20 mg/kg single, oral Recommended Dose: 20 mg/kg Route: oral Route: single Dose: 20 mg/kg Sources: |
unhealthy, 70.5 years (range: 53–84 years) Health Status: unhealthy Age Group: 70.5 years (range: 53–84 years) Sex: M+F Sources: |
| Urticaria | grade 3, 1.6% | 20 mg/kg single, oral Recommended Dose: 20 mg/kg Route: oral Route: single Dose: 20 mg/kg Sources: |
unhealthy, 70.5 years (range: 53–84 years) Health Status: unhealthy Age Group: 70.5 years (range: 53–84 years) Sex: M+F Sources: |
| Alanine aminotransferase increase | grade 3, 6.6% | 20 mg/kg single, oral Recommended Dose: 20 mg/kg Route: oral Route: single Dose: 20 mg/kg Sources: |
unhealthy, 70.5 years (range: 53–84 years) Health Status: unhealthy Age Group: 70.5 years (range: 53–84 years) Sex: M+F Sources: |
| Application site burning | 1 patient Disc. AE |
10 % 1 times / day multiple, topical Recommended Dose: 10 %, 1 times / day Route: topical Route: multiple Dose: 10 %, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
| Application site pain | 1 patient Disc. AE |
10 % 1 times / day multiple, topical Recommended Dose: 10 %, 1 times / day Route: topical Route: multiple Dose: 10 %, 1 times / day Sources: |
unhealthy Health Status: unhealthy Sex: M+F Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Fluorescence spectroscopy of normal mouse skin exposed to 5-aminolaevulinic acid and red light. | 2001-08-15 |
|
| Photodynamic therapy with topical delta-aminolaevulinic acid for the treatment of plantar warts. | 2001-08-15 |
|
| In vivo pharmacokinetics of protoporphyrin IX accumulation following intracutaneous injection of 5-aminolevulinic acid. | 2001-08-15 |
|
| Evaluation of protoporphyrin IX production, phototoxicity and cell death pathway induced by hexylester of 5-aminolevulinic acid in Reh and HPB-ALL cells. | 2001-08-10 |
|
| Antitumor effect of 5-aminolevulinic acid-mediated photodynamic therapy can be enhanced by the use of a low dose of photofrin in human tumor xenografts. | 2001-08-01 |
|
| Spectrophotometric microassay for delta-aminolevulinate dehydratase in dried-blood spots as confirmation for hereditary tyrosinemia type I. | 2001-08 |
|
| Correlation between lead exposure indicators and sister chromatid exchange (SCE) frequencies in lymphocytes from inorganic lead exposed workers. | 2001-08 |
|
| Peripheral neuropathy in chronic occupational inorganic lead exposure: a clinical and electrophysiological study. | 2001-08 |
|
| Recognition and transport characteristics of nonpeptidic compounds by basolateral peptide transporter in Caco-2 cells. | 2001-08 |
|
| Anticarcinogenic actions of melatonin which involve antioxidative processes: comparison with other antioxidants. | 2001-08 |
|
| Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity. | 2001-07-27 |
|
| Photosensitization and mechanism of cytotoxicity induced by the use of ALA derivatives in photodynamic therapy. | 2001-07-20 |
|
| [Are new treatments always effective ?]. | 2001-07-19 |
|
| The photosensitizing effect of the photoproduct of protoporphyrin IX. | 2001-07 |
|
| 5-Aminolaevulinic acid-mediated photodynamic therapy in multidrug resistant leukemia cells. | 2001-07 |
|
| Some articles should just not be published. | 2001-07 |
|
| Photodynamic therapy of actinic keratoses with topical aminolevulinic acid hydrochloride and fluorescent blue light. | 2001-07 |
|
| On the promoting action of tamoxifen in a model of hepatocarcinogenesis induced by p-dimethylaminoazobenzene in CF1 mice. | 2001-07 |
|
| Optimization of differential photodynamic effectiveness between normal and tumor urothelial cells using 5-aminolevulinic acid-induced protoporphyrin IX as sensitizer. | 2001-06-01 |
|
| Photobiological activity of exogenous and endogenous porphyrin derivatives in Escherichia coli and Enterococcus hirae cells. | 2001-06 |
|
| Effect of photodynamic therapy on urinary bladder function: an experimental study with rats. | 2001-06 |
|
| Topical 5-aminolaevulinic acid photodynamic therapy for tumour-stage mycosis fungoides. | 2001-06 |
|
| Systemic photodynamic therapy with aminolaevulinic acid delays the appearance of ultraviolet-induced skin tumours in mice. | 2001-06 |
|
| Role of 5-aminolevulinic acid in the diagnosis and treatment of superficial bladder cancer: improvement in diagnostic sensitivity. | 2001-06 |
|
| High efficiency of 5-aminolevulinate-photodynamic treatment using UVA irradiation. | 2001-06 |
|
| Clinical experience with 5-aminolevulinic acid and photodynamic therapy for refractory superficial bladder cancer. | 2001-06 |
|
| Expression of PEPT2 peptide transporter mRNA and protein in glial cells of rat dorsal root ganglia. | 2001-05-25 |
|
| Diagnosing cancer in vivo. | 2001-05-18 |
|
| Antioxidants inhibit indoleamine 2,3-dioxygenase in IFN-gamma-activated human macrophages: posttranslational regulation by pyrrolidine dithiocarbamate. | 2001-05-15 |
|
| Photomodification of the electrical properties of the plasma membrane: a comparison between 6 different membrane-active photosensitizers. | 2001-05-01 |
|
| Abortive assembly of succinate-ubiquinone reductase (complex II) in a ferrochelatase-deficient mutant of Escherichia coli. | 2001-05 |
|
| [Fluorescence cytology of the urinary bladder]. | 2001-05 |
|
| Photodynamic therapy for Bowen's disease (squamous cell carcinoma in situ) of the digit. | 2001-05 |
|
| A quantitative assessment of protoporphyrin IX metabolism and phototoxicity in human skin following dose-controlled delivery of the prodrugs 5-aminolaevulinic acid and 5-aminolaevulinic acid-n-pentylester. | 2001-05 |
|
| Fluorescence detection of cervical intraepithelial neoplasia for photodynamic therapy with the topical agents 5-aminolevulinic acid and benzoporphyrin-derivative monoacid ring. | 2001-05 |
|
| Zinc mesoporphyrin represses induced hepatic 5-aminolevulinic acid synthase and reduces heme oxygenase activity in a mouse model of acute hepatic porphyria. | 2001-05 |
|
| [Photodynamic therapy of dysplasias and early carcinomas in Barrett esophagus with a diode laser system--a pilot study]. | 2001-04-15 |
|
| Modulator of heme biosynthesis induces apoptosis in leukemia cells. | 2001-04 |
|
| The porphyrias: genetic and acquired aspects. | 2001-04 |
|
| Fluorescence staining of oral cancer using a topical application of 5-aminolevulinic acid: fluorescence microscopic studies. | 2001-04 |
|
| Topical photodynamic therapy at low fluence rates--theory and practice. | 2001-04 |
|
| Routine experimental system for defining conditions used in photodynamic therapy and fluorescence photodetection of (non-) neoplastic epithelia. | 2001-04 |
|
| Evaluation of different photosensitizers for use in photochemical gene transfection. | 2001-04 |
|
| Photodynamic therapy of feline superficial squamous cell carcinoma using topical 5-aminolaevulinic acid. | 2001-04 |
|
| Iontophoretic delivery of 5-aminolevulinic acid (ALA): effect of pH. | 2001-03 |
|
| [Experimental 5-aminolevulinic acid-induced photodynamic therapy (ALA-PDT) of oral carcinomas. Procedures in treatment of solid tumors and elucidation of cell death]. | 2001-03 |
|
| 5-Aminolevulinic acid inhibits [3H]muscimol binding to human and rat brain synaptic membranes. | 2001-02 |
|
| Melatonin prevents delta-aminolevulinic acid-induced oxidative DNA damage in the presence of Fe2+. | 2001-02 |
|
| An affordable, portable fluorescence imaging device for skin lesion detection using a dual wavelength approach for image contrast enhancement and aminolaevulinic acid-induced protoporphyrin IX. Part II. In vivo testing. | 2001 |
|
| An affordable, portable fluorescence imaging device for skin lesion detection using a dual wavelength approach for image contrast enhancement and aminolaevulinic acid-induced protoporphyrin IX. Part I. Design, spectral and spatial characteristics. | 2001 |
Patents
Sample Use Guides
In Vivo Use Guide
Curator's Comment: Can also be used orally for visualisation of malignant tissue during surgery for malignant glioma (WHO grade III and IV): the recommended dose is 20 mg 5-ALA HCl per kilogram body weight. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000744/WC500021790.pdf
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27764515
Curator's Comment: Glioma cells, seeded at the bottom of 96-well plates and incubated with ALA (10 ug/ml) for 6 h, were exposed to the sinusoidal US pulses with a resonance frequency of 1 MHz, 1000 µs duration, 0.4 duty-cycle, and average acoustic power varying from 2 W to 6 W. Ultrasound waves were generated by a flat circular piezoelectric transducer with a diameter of 25 mm. Cell viability was determined by MTT assay.
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
Created
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on
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Mon Mar 31 17:35:38 GMT 2025
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| Record UNII |
V35KBM8JGR
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Validated (UNII)
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| Record Version |
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| Classification Tree | Code System | Code | ||
|---|---|---|---|---|
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FDA ORPHAN DRUG |
761520
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NCI_THESAURUS |
C1420
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EMA ASSESSMENT REPORTS |
GLIOLAN (AUTHORIZED: GLIOMA)
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FDA ORPHAN DRUG |
236807
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FDA ORPHAN DRUG |
885522
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EU-Orphan Drug |
EU/3/02/121
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132969
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SUB21578
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DBSALT000934
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CHEMBL601
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V35KBM8JGR
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5451-09-2
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100000089584
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II-53
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18509
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C1849
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ALABEL
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PRIMARY | MARCH 2013 | ||
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261715
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123608
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m1713
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PRIMARY | Merck Index | ||
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DTXSID5045914
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226-679-5
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V35KBM8JGR
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1025715
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ALAGLIO
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PRIMARY | MARCH 2013 |
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PARENT -> SALT/SOLVATE |
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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ACTIVE MOIETY |
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