Details of the Drug

General Information of Drug (ID: DMDEA85)

Drug Name

Trimetrexate

Synonyms

TMQ; Trimetrexato; Trimetrexatum; JB 11; Jb-11; Trimetrexato [INN-Spanish]; Trimetrexatum [INN-Latin]; Trimetrexate (USAN/INN); Trimetrexate [USAN:BAN:INN]; 2,4-Diamino-5-methyl-6-((3,4,5-trimethoxyanilino)methyl)quinazoline; 5-Methyl-6-(((3,4,5-trimethoxyphenyl)amino)methyl)-2,4-quinazolinediamine; 5-methyl-6-({[3,4,5-tris(methyloxy)phenyl]amino}methyl)quinazoline-2,4-diamine; 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine; 6-[((3,4,5-Trimethoxyphenyl)amino)methyl]-5-methyl-2,4-quinazolinediamine

Indication

Disease Entry	ICD 11	Status	REF
Toxoplasmosis	1F57	Approved	[1]

Therapeutic Class

Antifungal Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

369.4

Topological Polar Surface Area (xlogp)

2.5

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance: The drug present in the plasma can be removed from the body at the rate of 0.77 mL/min/kg [3]
Elimination: 20% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 11 - 20 hours [3]
Metabolism: The drug is metabolized via the hepatic [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.30241 micromolar/kg/day [5]
Unbound Fraction: The unbound fraction of drug in plasma is 0.05% [3]
Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.77 L/kg [3]
Water Solubility: The ability of drug to dissolve in water is measured as 50 mg/mL [2]

Chemical Identifiers

Formula: C19H23N5O3
IUPAC Name: 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine
Canonical SMILES: CC1=C(C=CC2=C1C(=NC(=N2)N)N)CNC3=CC(=C(C(=C3)OC)OC)OC
InChI: InChI=1S/C19H23N5O3/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24)
InChIKey: NOYPYLRCIDNJJB-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 5583
ChEBI ID: CHEBI:9737
CAS Number: 52128-35-5
DrugBank ID: DB01157
TTD ID: D0Y7TS
VARIDT ID: DR01434

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[6], [7]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Toxoplasmosis

ICD Disease Classification

1F57

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Polypeptide deformylase (PDF)	DTT	PDF	8.87E-16	-0.54	-0.86
Breast cancer resistance protein (ABCG2)	DTP	BCRP	1.20E-13	-1.20E+00	-1.06E+00

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Trimetrexate (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[26]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[27]
Roflumilast	DMPGHY8	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Roflumilast.	Asthma [CA23]	[28]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Trimetrexate and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[29]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Cannabidiol.	Epileptic encephalopathy [8A62]	[28]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[30]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Trimetrexate and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[31]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Trimetrexate and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[32]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Trimetrexate and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[33]
Denosumab	DMNI0KO	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Denosumab.	Low bone mass disorder [FB83]	[34]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[35]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Idelalisib.	Mature B-cell leukaemia [2A82]	[36]
Tecfidera	DM2OVDT	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Tecfidera.	Multiple sclerosis [8A40]	[37]
Siponimod	DM2R86O	Major	Additive immunosuppressive effects by the combination of Trimetrexate and Siponimod.	Multiple sclerosis [8A40]	[26]
Fingolimod	DM5JVAN	Major	Additive immunosuppressive effects by the combination of Trimetrexate and Fingolimod.	Multiple sclerosis [8A40]	[38]
Ocrelizumab	DMEZ2KH	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Ocrelizumab.	Multiple sclerosis [8A40]	[39]
Ozanimod	DMT6AM2	Major	Additive immunosuppressive effects by the combination of Trimetrexate and Ozanimod.	Multiple sclerosis [8A40]	[28]
Omacetaxine mepesuccinate	DMPU2WX	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Omacetaxine mepesuccinate.	Myeloproliferative neoplasm [2A20]	[40]
Canakinumab	DM8HLO5	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Canakinumab.	Rheumatoid arthritis [FA20]	[41]
Rilonacept	DMGLUQS	Moderate	Additive immunosuppressive effects by the combination of Trimetrexate and Rilonacept.	Rheumatoid arthritis [FA20]	[41]
Golimumab	DMHZV7X	Major	Additive immunosuppressive effects by the combination of Trimetrexate and Golimumab.	Rheumatoid arthritis [FA20]	[42]
Anthrax vaccine	DM9GSWY	Moderate	Antagonize the effect of Trimetrexate when combined with Anthrax vaccine.	Sepsis [1G40-1G41]	[43]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Trimetrexate and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[28]
Valganciclovir	DMS2IUH	Moderate	Additive myelosuppressive effects by the combination of Trimetrexate and Valganciclovir.	Virus infection [1A24-1D9Z]	[26]
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⏷ Show the Full List of 24 DDI Information of This Drug

References

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27	Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
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29	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
30	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
31	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
32	Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
33	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
34	Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
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36	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
37	Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
38	Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
39	Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
40	Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
41	Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
42	Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
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