AMDINOCILLIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H23N3O3S
Molecular Weight	325.426
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SC(C)(C)[C@@H](N1C(=O)[C@H]2N=CN3CCCCCC3)C(O)=O

InChI

InChIKey=BWWVAEOLVKTZFQ-ISVUSNJMSA-N

InChI=1S/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/b16-9+/t10-,11+,13-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C15H23N3O3S
Molecular Weight	325.426
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Penicillin-binding protein 1A 45 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	Inhibitor 8297	0.224 µM [IC50]
UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae 3 Target ID: UniProtKB - Q7CRA4, pbp1b, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/25845878	Inhibitor 8297	0.147 µM [IC50]
UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae 3 Target ID: UniProtKB - Q8DNB6, pbp2a, Streptococcus pneumoniae Sources: https://www.ncbi.nlm.nih.gov/pubmed/7447421	Inhibitor 8297	30.0 nM [IC50]
UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis 3 Target ID: UniProtKB - A0A0E9DY48, PBP1, Chlamydia trachomatis Sources: https://www.ncbi.nlm.nih.gov/pubmed/11120983	Inhibitor 8297	0.6 nM [IC50]
UniProtKB - L0BBN1, pbp3, Haemophilus influenzae 3 Target ID: UniProtKB - L0BBN1, pbp3, Haemophilus influenzae Sources: https://www.ncbi.nlm.nih.gov/pubmed/6972731	Inhibitor 8297	3.7 nM [IC50]
Penicillin-binding protein 2 24 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	Inhibitor 8297	0.06 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Urinary tract infections 205 Sources: http://www.mims.com/india/drug/info/mecillinam?type=full&mtype=generic	Curative		Approved 8429	Mecillinam Approved Use Urinary tract infections Launch Date 4.72348787E11

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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: https://pubmed.ncbi.nlm.nih.gov/6311007 Page: p.83	healthy, 25 - 43 n = 12 Health Status: healthy Age Group: 25 - 43 Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/6311007 Page: p.83	Sources: https://pubmed.ncbi.nlm.nih.gov/6311007 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 Page: p.110	Other AEs: Diarrhea, Aspartate aminotransferase abnormal... Other AEs: Diarrhea (2.6%) Aspartate aminotransferase abnormal (10.52%) Alkaline phosphatase increased (7.9%) Sources: https://pubmed.ncbi.nlm.nih.gov/6310997 Page: p.110

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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 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: https://pubmed.ncbi.nlm.nih.gov/6310997 Page: p.110

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-3276	http://www.3bsc.com/index/pro_info.php?id=76217
AHH Chemical co.,ltd	MT-53466	http://www.ahhchemical.com/product/MT-53466.html
Aaron Chemicals	AR00JL85	http://www.aaronchem.com/prod/32887-01-7
Ambeed	A678129	https://www.ambeed.com/products/32887-01-7.html
Aurora Fine Chemicals LLC	A17.900.971	http://online.aurorafinechemicals.com/info?ID=A17.900.971
BLD Pharm	BD137305	http://www.bldpharm.com/products/32887-01-7.html
CSNpharm	CSN11365	https://www.csnpharm.com/products/mecillinam.html
Chem Scene	CS-0017618	http://www.chemscene.com/32887-01-7.html
Chemspace	CSSB00016995348	https://chem-space.com/CSSB00016995348
Glentham Life Sciences	GA6807	http://www.glentham.com/products/product/GA6807/
Lab Network	LN01267525	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01267525
MedChem Express	HY-A0269	https://www.medchemexpress.com/mecillinam.html
Selleck Chemicals	S6584	http://www.selleckchem.com/products/amdinocillin.html
Sigma-Aldrich	33447_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/33447?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
abcr GmbH	AB479645	http://www.abcr.com/shop/en/AB479645
eNovation Chemicals	D673770	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673770

PubMed

Title	Date	PubMed
Effect of perorally administered pivmecillinam on the normal oropharyngeal, intestinal and skin microflora.	2001 Jun	11450889
Urinary tract infections in Norway: bacterial etiology and susceptibility. A retrospective study of clinical isolates.	2001 Oct	11683794
[Antibiotic resistance of E coli isolated from healthy persons].	2001 Sep 3	11571862
[New molecules].	2001 Sep-Oct	11759148
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	12596863
Mecillinam susceptibility as an indicator of beta-lactamase production in Staphylococcus aureus.	2002 Feb	11952728
Mecillinam susceptibility of Auckland urinary isolates.	2002 Feb 8	11942520
Crystal structure of the Escherichia coli shikimate kinase I (AroK) that confers sensitivity to mecillinam.	2002 Jun 1	12001235
Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.	2003 Dec	14613955
A new method for normalized interpretation of antimicrobial resistance from disk test results for comparative purposes.	2003 Feb	12588332
Pivmecillinam--therapy of choice for lower urinary tract infection.	2003 Oct	14527775
Localizing cell division in spherical Escherichia coli by nucleoid occlusion.	2003 Sep 26	14553913
Shigella serotypes among hospitalized patients in urban Bangladesh and their antimicrobial resistance.	2004 Aug	15310182
Mecillinam has potent in vitro activity against Chlamydophila pneumoniae ATCC VR1310.	2004 Jun	15166212
Antimicrobial resistance in urinary bacterial isolates from pregnant women in rural Tanzania: implications for public health.	2005	15871165
Prevalence of Shigella species and their antimicrobial resistance patterns in Eastern Nepal.	2005 Dec	16599104
Uncomplicated urinary tract infections. Bacterial findings and efficacy of empirical antibacterial treatment.	2005 Jun	16036551
[Increasing antibiotic resistance in urinary tract infections].	2006 Apr 6	16619066
Activity of mecillinam against ESBL producers in vitro.	2006 Feb	16354745
Antimicrobial resistance among enterobacteriaceae causing uncomplicated urinary tract infections in Mauritius: consequences of past misuse of antibiotics.	2007 Apr	17434833
The diversity of multi-drug resistance profiles in tetracycline-resistant Vibrio species isolated from coastal sediments and seawater.	2007 Feb	17342058
A novel serovar of Shigella dysenteriae from patients with diarrhoea in Bangladesh.	2007 May	17446289
Evolutionary diversification of plant shikimate kinase gene duplicates.	2008 Dec	19057671
Transfer of antimicrobial resistance plasmids from Klebsiella pneumoniae to Escherichia coli in the mouse intestine.	2008 Nov	18703526
Endemic and epidemic lineages of Escherichia coli that cause urinary tract infections.	2008 Oct	18826822
RodZ, a new player in bacterial cell morphogenesis.	2009 Feb 4	19194484
[Clinical aspects and epidemiology of uncomplicated cystitis in women. German results of the ARESC Study].	2010 Feb	19943031
Septal and lateral wall localization of PBP5, the major D,D-carboxypeptidase of Escherichia coli, requires substrate recognition and membrane attachment.	2010 Jul	20545860
Do different susceptibility breakpoints affect the selection of antimicrobials for treatment of uncomplicated cystitis?	2010 Oct	21123159
Molecular and evolutionary bases of within-patient genotypic and phenotypic diversity in Escherichia coli extraintestinal infections.	2010 Sep 30	20941353

Patents

Sample Use Guides

In Vivo Use Guide

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

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).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:36:06 UTC 2023` Edited by `admin` on `Fri Dec 15 15:36:06 UTC 2023`
Record UNII	V10579P3QZ
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMDINOCILLIN

Official Name

English

FL 1060

Code

English

SELEXID

Brand Name

English

SELECIDIN

Brand Name

English

AMDINOCILLIN [USAN]

Common Name

English

(2S,5R,6R)-6-(((HEXAHYDRO-1H-AZEPIN-1-YL)METHYLENE)AMINO)-3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID.

Common Name

English

FL-1060

Code

English

MECILLINAM

Official Name

English

COACTIN

Brand Name

English

MECILLINAM [MART.]

Common Name

English

MECILLINAM [JAN]

Common Name

English

Mecillinam [WHO-DD]

Common Name

English

AMDINOCILLIN [MI]

Common Name

English

4-THIA-1-AZABICYCLO(3.2.0)HEPTANE-2-CARBOXYLIC ACID, 6-(((HEXAHYDRO-1H-AZEPIN-1-YL)METHYLENE)AMINO)-3,3-DIMETHYL-7-OXO-, (2S-(2.ALPHA.,5.ALPHA.,6.BETA.)0-

Common Name

English

SELEXIDIN

Brand Name

English

RO-10-9070

Code

English

mecillinam [INN]

Common Name

English

RO 10-9070

Code

English

AMDINOCILLIN [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1500