Details of the Drug

General Information of Drug (ID: DM5A31S)

Drug Name
TP-434
Synonyms
TP-038; TP-120; TP-170; TP-221; TP-271; TP-787; Tetracycline analogs (bacterial infection), Tetraphase Pharmaceuticals; Tetracycline derivatives (bacterial infection), Tetraphase Pharmaceuticals; Fluorocycline antibiotic (oral, bacterial infection), Tetraphase Pharmaceuticals; Tetracycline analogs (iv, antibiotic), Tetraphase Pharmaceuticals; TP-434 (oral, multidrug-resistant bacterial infections); TP-434 (oral, multidrug-resistant bacterial infections), Tetraphase Pharmaceuticals
Indication
Disease Entry ICD 11 Status REF
Intra-abdominal infection 1A40 Approved [1]
Influenza virus infection 1E30-1E32 Phase 2 [2]
Affected Organisms
Humans and other mammals
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 558.6
Logarithm of the Partition Coefficient (xlogp) 1
Rotatable Bond Count (rotbonds) 5
Hydrogen Bond Donor Count (hbonddonor) 6
Hydrogen Bond Acceptor Count (hbondacc) 11
ADMET Property
Clearance
The clearance of drug is 17.82 L/min [3]
Elimination
Following a single intravenous dose of radiolabeled eravacycline 60 mg, approximately 34% of the dose is excreted in urine and 47% in feces as unchanged eravacycline (20% in urine and 17% in feces) and metabolites []
Half-life
The concentration or amount of drug in body reduced by one-half in 20 hours []
Metabolism
The drug is metabolized via the CYP3A4 and FMO mediated oxidation []
Vd
The volume of distribution (Vd) of drug is 321 L []
Chemical Identifiers
Formula
C27H31FN4O8
IUPAC Name
(4S,4aS,5aR,12aR)-4-(dimethylamino)-7-fluoro-1,10,11,12a-tetrahydroxy-3,12-dioxo-9-[(2-pyrrolidin-1-ylacetyl)amino]-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
Canonical SMILES
CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=C(C(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)O)O)NC(=O)CN5CCCC5)F
InChI
InChI=1S/C27H31FN4O8/c1-31(2)20-13-8-11-7-12-14(28)9-15(30-16(33)10-32-5-3-4-6-32)21(34)18(12)22(35)17(11)24(37)27(13,40)25(38)19(23(20)36)26(29)39/h9,11,13,20,34-35,38,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33)/t11-,13-,20-,27-/m0/s1
InChIKey
AKLMFDDQCHURPW-ISIOAQNYSA-N
Cross-matching ID
PubChem CID
54726192
CAS Number
1207283-85-9
UNII
07896928ZC
DrugBank ID
DB12329
TTD ID
D0LZ7E
INTEDE ID
DR2504
ACDINA ID
D01056
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Bacterial 30S ribosomal RNA (Bact 30S rRNA) TTOVFH2 NOUNIPROTAC Inhibitor [1]
Bacterial Ribosome (Bact RIBS) TTND3XS NOUNIPROTAC Modulator [4]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4)
Main DME 		DE4LYSA CP3A4_HUMAN Substrate [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from TP-434 (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Troleandomycin DMUZNIG Minor Decreased metabolism of TP-434 caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [6]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Hydrochloric acid E00015 313 Acidulant
Mannitol E00103 6251 Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium hydroxide E00234 14798 Alkalizing agent
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Eravacycline 50 mg For Injection 50 mg For Injection Intravenous
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria.Expert Opin Pharmacother. 2018 Oct 22:1-13.
2 ClinicalTrials.gov (NCT01265784) Study to Compare TP-434 and Ertapenem in CA Complicated Intra-abdominal Infections. U.S. National Institutes of Health.
3 Connors KP, Housman ST, Pope JS, Russomanno J, Salerno E, Shore E, Redican S, Nicolau DP: Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women. Antimicrob Agents Chemother. 2014;58(4):2113-8. doi: 10.1128/AAC.02036-13. Epub 2014 Jan 27.
4 Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012 May;56(5):2559-64.
5 Mass balance and drug interaction potential of intravenous eravacycline administered to healthy subjects. Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: e01810-18.
6 Product Information. Xerava (eravacycline). Tetraphase Pharmaceuticals, Inc, Watertown, MA.