Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DM5A31S)

• Drug Name: TP-434 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 54726192
  CAS Number: CAS 1207283-85-9
  TTD Drug ID: DM5A31S
  INTEDE Drug ID: DR2504
  ACDINA Drug ID: D01056

Molecule-Related Drug Atlas

Drug(s) Targeting Bacterial 30S ribosomal RNA (Bact 30S rRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nitrofurazone	DMSM2KE	Skin burns	ME65.0	Approved	[5]
Gentamicin	DMKINJO	Bacteremia	1A73	Approved	[6]
Tobramycin	DMUI0CH	Bacteremia	1A73	Approved	[7]
Doxycycline	DM7ICNU	Acne vulgaris	ED80	Approved	[6]
Omadacycline	DMR2J95	Acute bacterial skin infection	1C41	Approved	[8]
Sarecycline	DMLZNIQ	Acne vulgaris	ED80	Approved	[9]
ME1100	DM39PSZ	Bacterial pneumonia	CA40.0	Phase 1	[10]
TP-6076	DM5RIT8	Enterobacteriaceae infection	MG50.C	Phase 1	[11]
TP-271	DM3PJSE	Pneumonia	CA40	Phase 1	[12]
TP 6076	DMD0NA1	Multidrug resistant infection	MG51	Phase 1	[11]

Drug(s) Targeting Bacterial Ribosome (Bact RIBS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OTB-658	DMFG7CC	Tuberculosis	1B10-1B14	Preclinical	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

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	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[4]

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] Target- and resistance-based mechanistic studies with TP-434, a novel fluorocycline antibiotic. Antimicrob Agents Chemother. 2012 May;56(5):2559-64.
• [4] Mass balance and drug interaction potential of intravenous eravacycline administered to healthy subjects. Antimicrob Agents Chemother. 2019 Feb 26;63(3). pii: e01810-18.
• [5] 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.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] 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.
• [8] Omadacycline Enters the Ring: A New Antimicrobial Contender.Pharmacotherapy. 2018 Dec;38(12):1194-1204.
• [9] 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.
• [10] ClinicalTrials.gov (NCT01961830) Intrapulmonary Pharmacokinetics of ME1100 in Healthy Volunteers. U.S. National Institutes of Health.
• [11] Clinical pipeline report, company report or official report of Tetraphase Pharmaceuticals.
• [12] Clinical pipeline report, company report or official report of Tetraphase Pharmaceuticals.
• [13] Clinical pipeline report, company report or official report of TB
• [14] 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.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] 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.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] 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.
• [19] 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.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] 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.
• [22] 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.