Details of the Drug

General Information of Drug (ID: DMDYA31)

Drug Name

Pretomanid

Synonyms

PA-824; 187235-37-6; Pretomanid; PA 824; PA824; UNII-2XOI31YC4N; (S)-PA 824; (S)-2-Nitro-6-((4-(trifluoromethoxy)benzyl)oxy)-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine; 2XOI31YC4N; CHEMBL227875; MMV688755; AK161427; (6S)-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine; (6S)-6,7-Dihydro-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-5H-imidazo[2,1-b][1,3]oxazine; Pretomanid [USAN:INN]; C14H12F3N3O5; PA-824(Pretomanid); AC1L9UFX; Pretomanid (USAN/INN); MLS006011141; SCHEMBL2983011

Indication

Disease Entry	ICD 11	Status	REF
Tuberculosis	1B10-1B14	Approved	[1]
Mycobacterium infection	1B10-1B21	Phase 3	[2]
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Affected Organisms

Mycobacterium tuberculosis

ATC Code

J04AK08: Pretomanid

J04AK: Other drugs for treatment of tuberculosis

J04A: DRUGS FOR TREATMENT OF TUBERCULOSIS

J04: ANTIMYCOBACTERIALS

J: ANTIINFECTIVES FOR SYSTEMIC USE

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

359.26

Logarithm of the Partition Coefficient (xlogp)

2.8

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 28.1 mgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1.7 mg/L [3]
Absorption Tmax: The time to maximum plasma concentration (Tmax) is 4-5 h [3]
Clearance: The clearance of drug is 4.8 +/- 0.2 L/h [4]
Elimination: An average of about 53% of the radioactive dose was found to be excreted in the urine [3]
Half-life: The concentration or amount of drug in body reduced by one-half in 16.9 - 17.4 hours [3]
Vd: The volume of distribution (Vd) of drug is 130 +/- 5 L [4]

Chemical Identifiers

Formula: C14H12F3N3O5
IUPAC Name: (6S)-2-nitro-6-[[4-(trifluoromethoxy)phenyl]methoxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine
Canonical SMILES: C1[C@@H](COC2=NC(=CN21)[N+](=O)[O-])OCC3=CC=C(C=C3)OC(F)(F)F
InChI: InChI=1S/C14H12F3N3O5/c15-14(16,17)25-10-3-1-9(2-4-10)7-23-11-5-19-6-12(20(21)22)18-13(19)24-8-11/h1-4,6,11H,5,7-8H2/t11-/m0/s1
InChIKey: ZLHZLMOSPGACSZ-NSHDSACASA-N

Cross-matching ID

PubChem CID: 456199
CAS Number: 187235-37-6
UNII: 2XOI31YC4N
DrugBank ID: DB05154
TTD ID: D02AYL
INTEDE ID: DR1338
ACDINA ID: D01360

Combinatorial Drugs (CBD)

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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
Mycobacterium Mycolic acid synthase (MycB cma)	TT08ESN	CMAS1_MYCTU ; CMAS2_MYCTU ; CMAS3_MYCTU	Inhibitor	[1]

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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 Pretomanid (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Arn-509	DMT81LZ	Major	Increased metabolism of Pretomanid caused by Arn-509 mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[6]
Pexidartinib	DMS2J0Z	Major	Increased metabolism of Pretomanid caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[6]
Lumacaftor	DMCLWDJ	Major	Increased metabolism of Pretomanid caused by Lumacaftor mediated induction of CYP450 enzyme.	Cystic fibrosis [CA25]	[7]
Cenobamate	DM8KLU9	Major	Increased metabolism of Pretomanid caused by Cenobamate mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[6]
Eslicarbazepine	DMZREFQ	Major	Increased metabolism of Pretomanid caused by Eslicarbazepine mediated induction of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[6]
Etravirine	DMGV8QU	Major	Increased metabolism of Pretomanid caused by Etravirine mediated induction of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[6]
PF-06463922	DMKM7EW	Major	Increased metabolism of Pretomanid caused by PF-06463922 mediated induction of CYP450 enzyme.	Lung cancer [2C25]	[6]
Dabrafenib	DMX6OE3	Major	Increased metabolism of Pretomanid caused by Dabrafenib mediated induction of CYP450 enzyme.	Melanoma [2C30]	[6]
Abametapir	DM2RX0I	Moderate	Decreased metabolism of Pretomanid caused by Abametapir mediated inhibition of CYP450 enzyme.	Pediculosis [1G00]	[8]
Lefamulin	DME6G97	Moderate	Decreased metabolism of Pretomanid caused by Lefamulin mediated inhibition of CYP450 enzyme.	Pneumonia [CA40]	[9]
Enzalutamide	DMGL19D	Major	Increased metabolism of Pretomanid caused by Enzalutamide mediated induction of CYP450 enzyme.	Prostate cancer [2C82]	[6]
Telotristat ethyl	DMDIYFZ	Major	Increased metabolism of Pretomanid caused by Telotristat ethyl mediated induction of CYP450 enzyme.	Small intestine developmental anomaly [DA90]	[7]
Pitolisant	DM8RFNJ	Major	Increased metabolism of Pretomanid caused by Pitolisant mediated induction of CYP450 enzyme.	Somnolence [MG42]	[6]
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⏷ Show the Full List of 13 DDI Information of This Drug

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

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium lauryl sulfate	E00464	3423265	Emulsifying agent; Modified-release agent; Penetration agent; Solubilizing agent; Surfactant; lubricant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Hydrophobic colloidal silica	E00285	24261	Anticaking agent; Emulsion stabilizing agent; Glidant; Suspending agent; Viscosity-controlling agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
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⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Pretomanid 200 mg tablet	200 mg	Tablet	Oral

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References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
2	ClinicalTrials.gov (NCT02342886) Shortening Treatment by Advancing Novel Drugs. U.S. National Institutes of Health.
3	Pretomanid FDA label, August 2019
4	Lyons MA: Modeling and Simulation of Pretomanid Pharmacokinetics in Pulmonary Tuberculosis Patients. Antimicrob Agents Chemother. 2018 Jun 26;62(7). pii: AAC.02359-17. doi: 10.1128/AAC.02359-17. Print 2018 Jul.
5	FDA briefing document - pretomanid tablet, 200 mg meeting of the antimicrobial drugs advisory committee (AMDAC).
6	Product Information. Pretomanid (pretomanid). The Global Alliance for TB Drug Development, New York, NY.
7	Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8. [PMID: 11959071]
8	Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
9	Product Information. Fycompa (perampanel). Eisai Inc, Teaneck, NJ.