CEFDITOREN PIVOXIL

US Previously Marketed

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C25H28N6O7S3
Molecular Weight	620.721
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12SCC(\C=C/C3=C(C)N=CS3)=C(N1C(=O)[C@H]2NC(=O)C(=N/OC)\C4=CSC(N)=N4)C(=O)OCOC(=O)C(C)(C)C

InChI

InChIKey=AFZFFLVORLEPPO-UVYJNCLZSA-N

InChI=1S/C25H28N6O7S3/c1-12-15(41-10-27-12)7-6-13-8-39-21-17(29-19(32)16(30-36-5)14-9-40-24(26)28-14)20(33)31(21)18(13)22(34)37-11-38-23(35)25(2,3)4/h6-7,9-10,17,21H,8,11H2,1-5H3,(H2,26,28)(H,29,32)/b7-6-,30-16-/t17-,21-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C25H28N6O7S3
Molecular Weight	620.721
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	2
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/dosage/cefditoren.html http://www.rxlist.com/spectracef-drug.htm http://www.wikidoc.org/index.php/Cefditoren

Cefditoren pivoxil is a semi-synthetic cephalosporin antibiotic for oral administration. It is a 3rd generation cephalosporin that is FDA approved for the treatment of acute bacterial exacerbation of chronic bronchitis, community acquired pneumonia, infection of skin and/or subcutaneous tissue, and pharyngitis/tonsillitis. Cefditoren is a cephalosporin with antibacterial activity against gram-positive and gram-negative pathogens. The bactericidal activity of cefditoren results from the inhibition of cell wall synthesis via affinity for penicillin-binding proteins (PBPs). Common adverse reactions include diarrhea, nausea and candida vaginitis. Co-administration of a single dose of an antacid which contained both magnesium (800 mg) and aluminum (900 mg) hydroxides or co-administration of a single dose of intravenously administered famotidine (20 mg) reduced the oral absorption of a single 400 mg dose of cefditoren pivoxil administered following a meal. Co-administration of probenecid with cefditoren pivoxil resulted in an increase in the plasma exposure of cefditoren.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Penicillin-binding protein 2B 10 Target ID: P0A3M6 Gene ID: 933948.0 Gene Symbol: penA Target Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11959556 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021222s012lbl.pdf	Inhibitor 8297
Penicillin-binding protein 1A 45 Target ID: Q8XJ01 Gene ID: 990276.0 Gene Symbol: pbpA Target Organism: Clostridium perfringens (strain 13 / Type A) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11959556 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021222s012lbl.pdf	Inhibitor 8297
Penicillin-binding protein 2X 5 Target ID: P59676 Gene ID: 934744.0 Gene Symbol: pbpX Target Organism: Streptococcus pneumoniae (strain ATCC BAA-255 / R6) Sources: https://www.ncbi.nlm.nih.gov/pubmed/11959556 \| https://www.ncbi.nlm.nih.gov/pubmed/17724158 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021222s012lbl.pdf	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Acute bacterial exacerbation of chronic bronchitis 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	Curative	Approved 8429	SPECTRACEF Approved Use SPECTRACEF® (cefditoren pivoxil) is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below. Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase producing strains), Streptococcus pneumoniae (penicillin susceptible strains only), or Moraxella catarrhalis (including ß-lactamase-producing strains). Community-Acquired Pneumonia caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis (including ß-lactamase producing strains). Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: SPECTRACEF® is effective in the eradication of Streptococcus pyogenes from the oropharynx. SPECTRACEF® has not been studied for the prevention of rheumatic fever following Streptococcus pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including ß-lactamase-producing strains) or Streptococcus pyogenes. To reduce the development of drug-resistant bacteria and maintain the effectiveness of SPECTRACEF® and other antibacterial drugs, SPECTRACEF® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 2001
Community-acquired pneumonia 47 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	Curative	Approved 8429	SPECTRACEF Approved Use SPECTRACEF® (cefditoren pivoxil) is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below. Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase producing strains), Streptococcus pneumoniae (penicillin susceptible strains only), or Moraxella catarrhalis (including ß-lactamase-producing strains). Community-Acquired Pneumonia caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis (including ß-lactamase producing strains). Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: SPECTRACEF® is effective in the eradication of Streptococcus pyogenes from the oropharynx. SPECTRACEF® has not been studied for the prevention of rheumatic fever following Streptococcus pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including ß-lactamase-producing strains) or Streptococcus pyogenes. To reduce the development of drug-resistant bacteria and maintain the effectiveness of SPECTRACEF® and other antibacterial drugs, SPECTRACEF® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 2001
Uncomplicated skin and skin-structure infections 21 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	Curative	Approved 8429	SPECTRACEF Approved Use SPECTRACEF® (cefditoren pivoxil) is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below. Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase producing strains), Streptococcus pneumoniae (penicillin susceptible strains only), or Moraxella catarrhalis (including ß-lactamase-producing strains). Community-Acquired Pneumonia caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis (including ß-lactamase producing strains). Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: SPECTRACEF® is effective in the eradication of Streptococcus pyogenes from the oropharynx. SPECTRACEF® has not been studied for the prevention of rheumatic fever following Streptococcus pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including ß-lactamase-producing strains) or Streptococcus pyogenes. To reduce the development of drug-resistant bacteria and maintain the effectiveness of SPECTRACEF® and other antibacterial drugs, SPECTRACEF® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 2001
Pharyngitis 31 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	Curative	Approved 8429	SPECTRACEF Approved Use SPECTRACEF® (cefditoren pivoxil) is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below. Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase producing strains), Streptococcus pneumoniae (penicillin susceptible strains only), or Moraxella catarrhalis (including ß-lactamase-producing strains). Community-Acquired Pneumonia caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis (including ß-lactamase producing strains). Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: SPECTRACEF® is effective in the eradication of Streptococcus pyogenes from the oropharynx. SPECTRACEF® has not been studied for the prevention of rheumatic fever following Streptococcus pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including ß-lactamase-producing strains) or Streptococcus pyogenes. To reduce the development of drug-resistant bacteria and maintain the effectiveness of SPECTRACEF® and other antibacterial drugs, SPECTRACEF® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 2001
Tonsillitis 36 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	Curative	Approved 8429	SPECTRACEF Approved Use SPECTRACEF® (cefditoren pivoxil) is indicated for the treatment of mild to moderate infections in adults and adolescents (12 years of age or older) which are caused by susceptible strains of the designated microorganisms in the conditions listed below. Acute Bacterial Exacerbation of Chronic Bronchitis caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase producing strains), Streptococcus pneumoniae (penicillin susceptible strains only), or Moraxella catarrhalis (including ß-lactamase-producing strains). Community-Acquired Pneumonia caused by Haemophilus influenzae (including ß-lactamase-producing strains), Haemophilus parainfluenzae (including ß-lactamase-producing strains), Streptococcus pneumoniae (penicillin-susceptible strains only), or Moraxella catarrhalis (including ß-lactamase producing strains). Pharyngitis/Tonsillitis caused by Streptococcus pyogenes. NOTE: SPECTRACEF® is effective in the eradication of Streptococcus pyogenes from the oropharynx. SPECTRACEF® has not been studied for the prevention of rheumatic fever following Streptococcus pyogenes pharyngitis/tonsillitis. Only intramuscular penicillin has been demonstrated to be effective for the prevention of rheumatic fever. Uncomplicated Skin and Skin-Structure Infections caused by Staphylococcus aureus (including ß-lactamase-producing strains) or Streptococcus pyogenes. To reduce the development of drug-resistant bacteria and maintain the effectiveness of SPECTRACEF® and other antibacterial drugs, SPECTRACEF® should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Launch Date 2001

C_max

Value	Dose	Co-administered	Analyte	Population
1.8 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CEFDITOREN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.6 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CEFDITOREN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
12% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021222s013s016lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		CEFDITOREN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 3 times / day steady, oral Studied dose Dose: 400 mg, 3 times / day Route: oral Route: steady Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17530036/	healthy, 18-30 years n = 8 Health Status: healthy Age Group: 18-30 years Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17530036/	Disc. AE: Gastrointestinal disturbance... AEs leading to discontinuation/dose reduction: Gastrointestinal disturbance (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/17530036/
200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2150 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2150 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	Disc. AE: Gastrointestinal disturbance, Diarrhoea... AEs leading to discontinuation/dose reduction: Gastrointestinal disturbance (2%) Diarrhoea (0.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/
400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2149 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2149 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	Disc. AE: Gastrointestinal disturbance, Diarrhoea... AEs leading to discontinuation/dose reduction: Gastrointestinal disturbance (3%) Diarrhoea (1.4%) Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/

AEs

AE	Significance	Dose	Population
Gastrointestinal disturbance	1 patient Disc. AE	400 mg 3 times / day steady, oral Studied dose Dose: 400 mg, 3 times / day Route: oral Route: steady Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17530036/	healthy, 18-30 years n = 8 Health Status: healthy Age Group: 18-30 years Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17530036/
Diarrhoea	0.7% Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2150 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2150 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/
Gastrointestinal disturbance	2% Disc. AE	200 mg 2 times / day steady, oral Recommended Dose: 200 mg, 2 times / day Route: oral Route: steady Dose: 200 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2150 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2150 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/
Diarrhoea	1.4% Disc. AE	400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2149 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2149 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/
Gastrointestinal disturbance	3% Disc. AE	400 mg 2 times / day steady, oral Recommended Dose: 400 mg, 2 times / day Route: oral Route: steady Dose: 400 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/	unhealthy, adult n = 2149 Health Status: unhealthy Condition: chronic bronchitis Age Group: adult Sex: unknown Population Size: 2149 Sources: https://pubmed.ncbi.nlm.nih.gov/11817976/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 270 UGT 192 OATP1B1 406 OATP2B1 104 BCRP 561	BCRP 75

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
BCRP 773	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1347436715300380	yes
P-gp 1650	supressor 155 Sources: https://www.sciencedirect.com/science/article/pii/S1347436715300380	yes

Drug as victim

Target	Modality	Activity
OATP2B1 104	substrate 3367 Sources: https://pubs.rsc.org/am/content/articlehtml/2017/ra/c7ra03537c	yes [Km 122.7 uM]
OATP1B1 406	substrate 3367 Sources: https://pubs.rsc.org/am/content/articlehtml/2017/ra/c7ra03537c	yes [Km 189.7 uM]
BCRP 561	substrate 3367 Sources: https://www.sciencedirect.com/science/article/pii/S1347436715300380	yes
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21222lbl.pdf#page=3 Page: 3.0	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/21222lbl.pdf#page=3 Page: 3.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:59343	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:59343
ChemicalBook	CB2874737	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2874737
ZINC	ZINC000004215234	http://zinc15.docking.org/substances/ZINC000004215234

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

Acute bacterial exacerbation of chronic bronchitis: 400 mg twice a day for 10 days. Community-acquired pneumonia: 400 mg twice a day for 14 days Tonsillitis/Pharyngitis and Uncomplicated Skin or Soft Tissue Infection: 200 mg twice a day for 10 days

Route of Administration: Oral

In Vitro Use Guide

The level of cefditoren activity against S. pneumoniae (MIC(90,) 0.5 microg/mL) was superior to all marketed oral cephalosporins and at least equal to amoxicillin +/- clavulanate. H. influenzae (MIC(90,) 0.016-0.03 microg/mL) and M. catarrhalis (MIC(90,) 0.06-0.5 microg/mL) were also very susceptible to cefditoren. cefditoren was active against oxacillin-susceptible staphylococci (MIC(90,) < or = 1 microg/mL) at a level comparable to cefuroxime axetil, cefaclor or cefprozil.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:57:03 GMT 2023` Edited by `admin` on `Fri Dec 15 15:57:03 GMT 2023`
Record UNII	78THA212DH
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CEFDITOREN PIVOXIL

Official Name

English

CEFDITOREN PIVOXIL [USAN]

Common Name

English

CEFDITOREN PIVOXIL [JAN]

Common Name

English

MEIACT

Brand Name

English

CEFDITOREN PIVALOYLOXYMETHYL ESTER

Common Name

English

SPECTRACEF

Brand Name

English

ME1207

Code

English

CEFDITOREN PIVALOYLOXYMETHYL ESTER [MI]

Common Name

English

CEFDITOREN PIVOXIL [MART.]

Common Name

English

(+)-(6R,7R)-7-(2-(2-AMINO-4-THIAZOLYL)GLYOXYLAMIDO)-3-((Z)-2-(4-METHYL-5-THIAZOLYL)VINYL)-8-OXO-5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLATE PIVALOYLOXY METHYL ESTER, 7(SUP 2)-(Z)-(O-METHYLOXIME)

Common Name

English

Cefditoren pivoxil [WHO-DD]

Common Name

English

ME-1207

Code

English

NSC-759098

Code

English

CEFDITOREN PIVOXIL [VANDF]

Common Name

English

CDTR-PI

Code

English

CEFDITOREN PIVOXIL [ORANGE BOOK]

Common Name

English

5-THIA-1-AZABICYCLO(4.2.0)OCT-2-ENE-2-CARBOXYLIC ACID, 7(((2Z)-(2-AMINO-4-THIAZOLYL)(METHOXYIMINO)ACETYL)AMINO)-3-((1Z)-2-(4-METHYL-5-THIAZOLYL)ETHENYL)-8-OXO-, (2,2-DIMETHYL-1-OXOPROPOXY)METHYL ESTER, (6R,7R)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C357