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Details

Stereochemistry ABSOLUTE
Molecular Formula C29H39N5O8.ClH
Molecular Weight 622.11
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIGECYCLINE HYDROCHLORIDE

SMILES

Cl.[H][C@@]12CC3=C(C=C(NC(=O)CNC(C)(C)C)C(O)=C3C(=O)C1=C(O)[C@]4(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@]4([H])C2)N(C)C

InChI

InChIKey=ATIINCUPZOADER-KXLOKULZSA-N
InChI=1S/C29H39N5O8.ClH/c1-28(2,3)31-11-17(35)32-15-10-16(33(4)5)13-8-12-9-14-21(34(6)7)24(38)20(27(30)41)26(40)29(14,42)25(39)18(12)23(37)19(13)22(15)36;/h10,12,14,21,31,36,38-39,42H,8-9,11H2,1-7H3,(H2,30,41)(H,32,35);1H/t12-,14-,21-,29-;/m0./s1

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB00560 https://en.wikipedia.org/wiki/Tigecycline

Tigecycline (INN) is an antibiotic used to treat a number of bacterial infections. It is a first in class glycylcycline that is administered intravenously. For the treatment of infections caused by susceptible strains of the designated microorganisms in the following conditions: Complicated skin and skin structure infections caused by Escherichia coli, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible and -resistant isolates), Streptococcus agalactiae, Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Streptococcus pyogenes and Bacteroides fragilis. Complicated intra-abdominal infections caused by Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Enterococcus faecalis (vancomycin-susceptible isolates only), Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus anginosus grp. (includes S. anginosus, S. intermedius, and S. constellatus), Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Clostridium perfringens, and Peptostreptococcus micros. Tigecycline, a glycylcycline, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. In general, tigecycline is considered bacteriostatic; however, TYGACIL has demonstrated bactericidal activity against isolates of S. pneumoniae and L. pneumophila. In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterials.

CNS Activity

CNS Penetrant
2554
Curator's Comment: On average, the systemic exposure of tigecycline in bone, SF and CSF ranged from 11% to 41% of serum concentrations.

Originator

Wyeth
116
Curator's Comment: # Wyeth Pharmaceuticals

Approval Year

2005
131
Targets

Targets

Primary TargetPharmacologyConditionPotency
Binding Agent
1064
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8429
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

2006
Curative
Approved
8429
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

2006
Curative
Approved
8429
TYGACIL

Approved Use

is a tetracycline-class antibacterial drug indicated in patients 18 years of age and older for: Complicated skin and skin structure infections; Complicated intra-abdominal infections; Community-acquired bacterial pneumonia; Limitations of Use: TYGACIL is not indicated for treatment of diabetic foot infection or hospital-acquired pneumonia, including ventilator-associated pneumonia

Launch Date

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.63 μg/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
4.7 μg × h/mL
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
7.64 mg*h/L
Clinical Trial
https://clinicaltrials.gov/ct2/show/NCT01560143
100 mg single, intravenous
dose: 100 mg
route of administration: intravenous
experiment type: single
co-administered:
TIGECYCLINE serum
Homo sapiens
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
42.4 h
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
11%
DRUG LABEL
https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021821s026s031lbl.pdf
50 mg 2 times / day multiple, intravenous
dose: 50 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
TIGECYCLINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg 2 times / day multiple, intravenous
Highest studied dose
Dose: 100 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Disc. AE: Gastrointestinal disorder (NOS)...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal disorder (NOS) (50%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
300 mg single, intravenous
Highest studied dose
Dose: 300 mg
Route: intravenous
Route: single
Dose: 300 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
DLT: Gastrointestinal disorder NOS...
Dose limiting toxicities:
Gastrointestinal disorder NOS
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (50%)
Vomiting (50%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea
Vomiting
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
Disc. AE: Nausea, Vomiting...
AEs leading to
discontinuation/dose reduction:
Nausea (1%)
Vomiting (1%)
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Disc. AE: Anaphylaxis, Anaphylactoid reaction...
AEs leading to
discontinuation/dose reduction:
Anaphylaxis
Anaphylactoid reaction
Hepatic dysfunction NOS
Liver failure
Pancreatitis (grade 5)
Fetal damage
Tooth discoloration
Diarrhea, Clostridium difficile
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
AEs

AEs

AESignificanceDosePopulation
Gastrointestinal disorder (NOS) 50%
Disc. AE
100 mg 2 times / day multiple, intravenous
Highest studied dose
Dose: 100 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 100 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Gastrointestinal disorder NOS DLT
300 mg single, intravenous
Highest studied dose
Dose: 300 mg
Route: intravenous
Route: single
Dose: 300 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Nausea 50%
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Vomiting 50%
100 mg single, intravenous
MTD
Dose: 100 mg
Route: intravenous
Route: single
Dose: 100 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Nausea
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Vomiting
200 mg single, intravenous
MTD
Dose: 200 mg
Route: intravenous
Route: single
Dose: 200 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
healthy
n = 6
Health Status: healthy
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/15616299
Page: p.223
Nausea 1%
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
Vomiting 1%
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
unhealthy
n = 3788
Health Status: unhealthy
Condition: Complicated skin and skin structure infections
Population Size: 3788
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.10
Anaphylactoid reaction Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Anaphylaxis Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Diarrhea, Clostridium difficile Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Fetal damage Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Hepatic dysfunction NOS Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Liver failure Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Tooth discoloration Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Pancreatitis grade 5
Disc. AE
50 mg 2 times / day multiple, intravenous
Recommended
Dose: 50 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 50 mg, 2 times / day
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Complicated skin and skin structure infections|Complicated intra-abdominal infections|Community-acquired bacterial pneumonia
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021821s021lbl.pdf
Page: p.1
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP2C19
1478

CYP2C8
911

CYP1A2
1524

P-gp
1461
P-gp
1537
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP1A2
1692
 no [IC50 >100 uM]
CYP2C19
1553
 no [IC50 >100 uM]
CYP2C8
965
 no [IC50 >100 uM]
CYP2C9
1819
 no [IC50 >100 uM]
CYP2D6
1891
 no [IC50 >100 uM]
CYP3A4
1925
 no [IC50 >100 uM]
P-gp
1650
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 inconclusive
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
Sourcing

Sourcing

Vendor/AggregatorIDURL
ChEBI
CHEBI:149836
https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:149836
ChemicalBook
CB6248215
https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6248215
MolPort
MolPort-009-199-379
https://www.molport.com/shop/molecule-link/MolPort-009-199-379
Selleck Chemicals
Tigecycline
http://www.selleckchem.com/products/Tigecycline.html
ZINC
ZINC000014879972
http://zinc15.docking.org/substances/ZINC000014879972
eMolecules
6719081
https://www.emolecules.com/cgi-bin/more?vid=6719081
PubMed

PubMed

TitleDatePubMed
Comparison of the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, minocycline, and doxycycline against isolates of nontuberculous mycobacteria.
2002 Oct
Tigecycline: first of a new class of antimicrobial agents.
2006 Aug
Tigecycline: a new glycylcycline antimicrobial agent.
2006 Jul 1
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.
2015 May 18
Patents

Patents

08252946
2
20030166585
2
JP2007515411A
2
JP2009191083A
2
JP2010024252A
2

Sample Use Guides

In Vivo Use Guide
Initial dose of 100 mg, followed by 50 mg every 12 hours administered intravenously over approximately 30 to 60 minutes. Severe hepatic impairment (Child Pugh C): Initial dose of 100 mg followed by 25 mg every 12 hours.
Route of Administration: Intravenous
In Vitro Use Guide
Among the tested gram-positive isolates, tigecycline was most active as reflected by MIC50/MIC90 values against S. pyogenes (0.03/0.03 μg/ml) and S. pneumoniae (0.015/0.03 μg/ml), followed by S. aureus (0.12/0.25 μg/ml) and E. faecalis (0.12/0.5 μg/ml)
Name Type Language
TIGECYCLINE HYDROCHLORIDE
Common Name English
TIGECYCLINE MONOHYDROCHLORIDE
Common Name English
2-NAPHTHACENECARBOXAMIDE, 4,7-BIS(DIMETHYLAMINO)-9-((2-((1,1-DIMETHYLETHYL)AMINO)ACETYL)AMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,10,12,12A-TETRAHYDROXY-1,11-DIOXO-, HYDROCHLORIDE (1:1), (4S,4AS,5AR,12AS)-
Systematic Name English
Code System Code Type Description
FDA UNII
7F4TZ17Y3R
Created by admin on Sat Dec 16 15:19:27 GMT 2023 , Edited by admin on Sat Dec 16 15:19:27 GMT 2023
PRIMARY
CAS
197654-04-9
Created by admin on Sat Dec 16 15:19:27 GMT 2023 , Edited by admin on Sat Dec 16 15:19:27 GMT 2023
PRIMARY
ACTIVE MOIETY
Structure of TIGECYCLINE
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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