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]
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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
DrugBank ID: DB12329
TTD ID: D0LZ7E
INTEDE ID: DR2504
ACDINA ID: D01056

Repurposed Drugs (RPD)

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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]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[5]

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Molecular Interaction Atlas (MIA)

MIA Detail

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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]
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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
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Eravacycline 50 mg For Injection	50 mg	For Injection	Intravenous

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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.