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]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 3

Molecular Weight (mw)

558.6

Topological Polar Surface Area (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 [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 20 hours [5]
Metabolism: The drug is metabolized via the CYP3A4 and FMO mediated oxidation [5]
Vd: The volume of distribution (Vd) of drug is 321 L [4]

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

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	[6]

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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	[7]

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Molecular Interaction Atlas (MIA)

MIA Detail

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]	[25]
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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

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	An FDA phase I clinical trial of quinacrine sterilization (QS). Int J Gynaecol Obstet. 2003 Oct;83 Suppl 2:S45-9.
5	FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
6	Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012 May;56(5):2559-64.
7	Mass balance and drug interaction potential of intravenous eravacycline administered to healthy subjects. Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: e01810-18.
8	Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
9	Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
10	Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
11	Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
12	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
13	Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
14	Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
15	The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
16	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
17	The antibiotic Furvina targets the P-site of 30S ribosomal subunits and inhibits translation initiation displaying start codon bias. Nucleic Acids Res. 2012 Nov 1;40(20):10366-74.
18	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
19	Mechanism of action of aminoglycoside antibiotics.Binding studies of tobramycin and its 6'-N-acetyl derivative to the bacterial ribosome and its subunits.Eur J Biochem.1979 Dec;102(1):73-81.
20	Omadacycline Enters the Ring: A New Antimicrobial Contender.Pharmacotherapy. 2018 Dec;38(12):1194-1204.
21	Microbiological Profile of Sarecycline, a Novel Targeted Spectrum Tetracycline for the Treatment of Acne Vulgaris.Antimicrob Agents Chemother. 2018 Dec 21;63(1). pii: e01297-18.
22	ClinicalTrials.gov (NCT01961830) Intrapulmonary Pharmacokinetics of ME1100 in Healthy Volunteers. U.S. National Institutes of Health.
23	Clinical pipeline report, company report or official report of Tetraphase Pharmaceuticals.
24	Clinical pipeline report, company report or official report of Tetraphase Pharmaceuticals.
25	Product Information. Xerava (eravacycline). Tetraphase Pharmaceuticals, Inc, Watertown, MA.