Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C21H33N3O5S.ClH |
Molecular Weight | 476.03 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 1 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2N=CN3CCCCCC3)C(=O)OCOC(=O)C(C)(C)C
InChI
InChIKey=UHPXMYLONAGUPC-YKBWBZKYSA-N
InChI=1S/C21H33N3O5S.ClH/c1-20(2,3)19(27)29-13-28-18(26)15-21(4,5)30-17-14(16(25)24(15)17)22-12-23-10-8-6-7-9-11-23;/h12,14-15,17H,6-11,13H2,1-5H3;1H/b22-12+;/t14-,15+,17-;/m1./s1
DescriptionSources: http://www.drugbank.ca/drugs/DB01163Curator's Comment: Description was created based on several sources, including
http://www.mims.com/india/drug/info/mecillinam?type=full&mtype=generic and https://www.ncbi.nlm.nih.gov/pubmed/3885172
Sources: http://www.drugbank.ca/drugs/DB01163
Curator's Comment: Description was created based on several sources, including
http://www.mims.com/india/drug/info/mecillinam?type=full&mtype=generic and https://www.ncbi.nlm.nih.gov/pubmed/3885172
Amdinocillin is a novel, semisynthetic penicillin effective against many gram-negative bacteria. The antibacterial activity of amdinocillin is derived from its ability to bind specifically and avidly to Penicillin Binding Protein-2 (PBP 2). Amdinocillin is active alone against many gram-negative organisms. Pseudomonas and non-fermenting gram-negative bacteria, however, are usually resistant. Amdinocillin, in combination with many beta-lactams, exhibits marked synergy against many enterobacteriaceae. No such synergy can be demonstrated for gram-positive organisms or pseudomonas species. Amdinocillin is not beta-lactamase stable. Organisms which produce high levels of plasma-mediated beta-lactamase are resistant to the drug. Used in the treatment of urinary tract infections caused by some strains of E. coli and klebsiella and enterobacter species. Used mainly against Gram negative organisms. Amdinocillin is not available in the United States.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6274562
Curator's Comment: Poor penetration in humans
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/232703
Curator's Comment: Mecillinam (Amdinocillin) developed by Leo Pharmaceuticals Balleherup, Denmark),
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q8DR59 Gene ID: 934791.0 Gene Symbol: pbpA Target Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845878 |
0.224 µM [IC50] | ||
Target ID: UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845878 |
0.147 µM [IC50] | ||
Target ID: UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/7447421 |
30.0 nM [IC50] | ||
Target ID: UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120983 |
0.6 nM [IC50] | ||
Target ID: UniProtKB - L0BBN1, pbp3, Haemophilus influenzae Sources: https://www.ncbi.nlm.nih.gov/pubmed/6972731 |
3.7 nM [IC50] | ||
Target ID: P0AD65 Gene ID: 945240.0 Gene Symbol: mrdA Target Organism: Escherichia coli (strain K12) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25733506 |
0.06 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Mecillinam Approved UseUrinary tract infections Launch Date1984 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
87.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intravenous dose: 15 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
3.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
4.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
49.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/ |
10 mg/kg bw 6 times / day steady-state, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
26.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intramuscular dose: 10 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
29.6 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intramuscular dose: 15 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
49.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
112.97 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intravenous dose: 15 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
10 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
7.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
8.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.7 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
47.94 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intramuscular dose: 10 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
72.15 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intramuscular dose: 15 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
58.81 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.886 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intravenous dose: 15 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3377469/ |
400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
52.39 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/ |
10 mg/kg bw 6 times / day steady-state, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: STEADY-STATE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
54.38 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6282208/ |
10 mg/kg bw single, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
0.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intramuscular dose: 10 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.859 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
15 mg/kg bw single, intramuscular dose: 15 mg/kg bw route of administration: Intramuscular experiment type: SINGLE co-administered: |
AMDINOCILLIN serum | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.888 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6311087/ |
10 mg/kg bw single, intravenous dose: 10 mg/kg bw route of administration: Intravenous experiment type: SINGLE co-administered: |
AMDINOCILLIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg single, intravenous Highest studied dose Dose: 500 mg Route: intravenous Route: single Dose: 500 mg Sources: Page: p.83 |
healthy, 25 - 43 n = 12 Health Status: healthy Age Group: 25 - 43 Population Size: 12 Sources: Page: p.83 |
|
10 mg/kg 4 times / day multiple, intravenous Studied dose Dose: 10 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 10 mg/kg, 4 times / day Sources: Page: p.110 |
unhealthy, 25-94 n = 38 Health Status: unhealthy Condition: gram-negative baciliary infections Age Group: 25-94 Sex: M+F Population Size: 38 Sources: Page: p.110 |
Other AEs: Diarrhea, Aspartate aminotransferase abnormal... Other AEs: Diarrhea (2.6%) Sources: Page: p.110Aspartate aminotransferase abnormal (10.52%) Alkaline phosphatase increased (7.9%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Aspartate aminotransferase abnormal | 10.52% | 10 mg/kg 4 times / day multiple, intravenous Studied dose Dose: 10 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 10 mg/kg, 4 times / day Sources: Page: p.110 |
unhealthy, 25-94 n = 38 Health Status: unhealthy Condition: gram-negative baciliary infections Age Group: 25-94 Sex: M+F Population Size: 38 Sources: Page: p.110 |
Diarrhea | 2.6% | 10 mg/kg 4 times / day multiple, intravenous Studied dose Dose: 10 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 10 mg/kg, 4 times / day Sources: Page: p.110 |
unhealthy, 25-94 n = 38 Health Status: unhealthy Condition: gram-negative baciliary infections Age Group: 25-94 Sex: M+F Population Size: 38 Sources: Page: p.110 |
Alkaline phosphatase increased | 7.9% | 10 mg/kg 4 times / day multiple, intravenous Studied dose Dose: 10 mg/kg, 4 times / day Route: intravenous Route: multiple Dose: 10 mg/kg, 4 times / day Sources: Page: p.110 |
unhealthy, 25-94 n = 38 Health Status: unhealthy Condition: gram-negative baciliary infections Age Group: 25-94 Sex: M+F Population Size: 38 Sources: Page: p.110 |
PubMed
Title | Date | PubMed |
---|---|---|
Penicillin-binding proteins and role of amdinocillin in causing bacterial cell death. | 1983 Aug 29 |
|
Efficacy of amdinocillin and lack of nephrotoxicity when combined with a second beta-lactam antibiotic for therapy of serious gram-negative bacillary infections. | 1983 Aug 29 |
|
Microbiological evaluation of a commercial transport system for urine samples. | 2002 |
|
Validation of FLEXICULT SSI-Urinary Kit for use in the primary health care setting. | 2002 |
|
Novel S-benzylisothiourea compound that induces spherical cells in Escherichia coli probably by acting on a rod-shape-determining protein(s) other than penicillin-binding protein 2. | 2002 Dec |
|
Mecillinam susceptibility as an indicator of beta-lactamase production in Staphylococcus aureus. | 2002 Feb |
|
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam. | 2002 Jun 1 |
|
Susceptibility of Danish Escherichia coli strains isolated from urinary tract infections and bacteraemia, and distribution of sul genes conferring sulphonamide resistance. | 2002 Oct |
|
[Urinary tract pathogens in uncomplicated lower urinary tract infections in women in Norway]. | 2003 Aug 14 |
|
Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection. | 2003 Dec |
|
A new method for normalized interpretation of antimicrobial resistance from disk test results for comparative purposes. | 2003 Feb |
|
Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. | 2003 Jan |
|
An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project. | 2003 Jan |
|
Identification of the CysB-regulated gene, hslJ, related to the Escherichia coli novobiocin resistance phenotype. | 2003 Jul 29 |
|
Null mutations in the essential gene yrfF (mucM) are not lethal in rcsB, yojN or rcsC strains of Salmonella enterica serovar Typhimurium. | 2003 May 16 |
|
Pivmecillinam--therapy of choice for lower urinary tract infection. | 2003 Oct |
|
Prevalence and antimicrobial susceptibility of pathogens in uncomplicated cystitis in Europe. The ECO.SENS study. | 2003 Oct |
|
Localizing cell division in spherical Escherichia coli by nucleoid occlusion. | 2003 Sep 26 |
|
Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance. | 2004 Aug |
|
Urinary concentrations and urine ex-vivo effect of mecillinam and sulphamethizole. | 2004 Jan |
|
Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC VR1310. | 2004 Jun |
|
Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health. | 2005 |
|
Prevalence of Shigella species and their antimicrobial resistance patterns in Eastern Nepal. | 2005 Dec |
|
Uncomplicated urinary tract infections. Bacterial findings and efficacy of empirical antibacterial treatment. | 2005 Jun |
|
Susceptibility testing of urinary isolates of Escherichia coli to mecillinam using NCCLS methodology. | 2005 Mar |
|
Intracellular persistence of Escherichia coli in urinary bladders from mecillinam-treated mice. | 2005 Mar |
|
Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli. | 2005 May |
|
Isolation and characterization of provisional serovar Shigella boydii E16553 from diarrhoeal patients in Bangladesh. | 2005 May |
|
Partition of old murein in small patches over the entire wall of E. coli cells forced to grow as a coccoid. | 2006 Apr |
|
The emerging strains of Shigella dysenteriae type 2 in Bangladesh are clonal. | 2006 Dec |
|
Activity of mecillinam against ESBL producers in vitro. | 2006 Feb |
|
High-level resistance to mecillinam produced by inactivation of soluble lytic transglycosylase in Salmonella enterica serovar Typhimurium. | 2006 Mar |
|
The diversity of multi-drug resistance profiles in tetracycline-resistant Vibrio species isolated from coastal sediments and seawater. | 2007 Feb |
|
Increasing spectrum in antimicrobial resistance of Shigella isolates in Bangladesh: resistance to azithromycin and ceftriaxone and decreased susceptibility to ciprofloxacin. | 2007 Jun |
|
Evolutionary diversification of plant shikimate kinase gene duplicates. | 2008 Dec |
|
In vitro interaction between mecillinam and piperacillin-tazobactam in the presence of azithromycin against members of the Enterobacteriaceae family and Pseudomonas aeruginosa. | 2008 Jan |
|
Dissemination of multidrug-resistant bacteria into the Arctic. | 2008 Jan |
|
Transfer of antimicrobial resistance plasmids from Klebsiella pneumoniae to Escherichia coli in the mouse intestine. | 2008 Nov |
|
Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy. | 2008 Nov |
|
Endemic and epidemic lineages of Escherichia coli that cause urinary tract infections. | 2008 Oct |
|
Multi-resistant Escherichia coli and mycotic aneurysm: two case reports. | 2009 Mar 10 |
|
Bend into shape. | 2009 May 6 |
|
The ARESC study: an international survey on the antimicrobial resistance of pathogens involved in uncomplicated urinary tract infections. | 2009 Nov |
|
Empiric antibiotic therapy in acute uncomplicated urinary tract infections and fluoroquinolone resistance: a prospective observational study. | 2009 Oct 24 |
|
[Clinical aspects and epidemiology of uncomplicated cystitis in women. German results of the ARESC Study]. | 2010 Feb |
|
Molecular characterisation of trimethoprim resistance in Escherichia coli and Klebsiella pneumoniae during a two year intervention on trimethoprim use. | 2010 Feb 16 |
|
Septal and lateral wall localization of PBP5, the major D,D-carboxypeptidase of Escherichia coli, requires substrate recognition and membrane attachment. | 2010 Jul |
|
Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis? | 2010 Oct |
|
Extended-spectrum β-lactamases in Gram Negative Bacteria. | 2010 Sep |
|
Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections. | 2010 Sep 30 |
Patents
Sample Use Guides
Parenteral
Urinary tract infections
Adult: 800 mg every 6-8 hr by IM, slow IV inj or IV infusion. Severe infections: Up to 60 mg/kg/day.
Route of Administration:
Parenteral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120983
Amdinocillin (Mecillinam) selectively inhibited PBP1, with a 50% inhibitory concentration for PBP1 binding (0.2 ug/ml) similar to the MIC (0.1 ug/ml) and minimum bactericidal concentration (0.25 ug/ml).
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Code System | Code | Type | Description | ||
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SUB03884MIG
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102745
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51213
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32887-03-9
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CHEMBL1650818
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m1654
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DBSALT001943
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48FX7N21H2
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251-278-7
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DTXSID1045453
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100000091362
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115162
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ACTIVE MOIETY
PARENT (SALT/SOLVATE)
SUBSTANCE RECORD