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
Affected Organisms
Bacteria and protozoaHumans and other mammalsPneumocystis carinii
ATC Code
P01AX07: Trimetrexate
P01AX: Other agents against amoebiasis and other protozoal diseases
P01A: AGENTS AGAINST AMOEBIASIS AND OTHER PROTOZOAL DISEASES
P01: ANTIPROTOZOALS
P: ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 369.4
Logarithm of the Partition Coefficient (xlogp) 2.5
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
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 []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 3.30241 micromolar/kg/day [4]
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
CHEMBL119
CAS Number
52128-35-5
UNII
UPN4ITI8T4
DrugBank ID
DB01157
TTD ID
D0Y7TS
VARIDT ID
DR01434
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

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 [5]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [6]
Molecular Interaction Atlas (MIA) 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) 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] [7]
Bedaquiline DM3906J Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Bedaquiline. Antimicrobial drug resistance [MG50-MG52] [8]
Roflumilast DMPGHY8 Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Roflumilast. Asthma [CA23] [9]
Pexidartinib DMS2J0Z Major Increased risk of hepatotoxicity by the combination of Trimetrexate and Pexidartinib. Bone/articular cartilage neoplasm [2F7B] [10]
Cannabidiol DM0659E Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Cannabidiol. Epileptic encephalopathy [8A62] [9]
Brentuximab vedotin DMWLC57 Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Brentuximab vedotin. Hodgkin lymphoma [2B30] [11]
Mipomersen DMGSRN1 Major Increased risk of hepatotoxicity by the combination of Trimetrexate and Mipomersen. Hyper-lipoproteinaemia [5C80] [12]
Teriflunomide DMQ2FKJ Major Increased risk of hepatotoxicity by the combination of Trimetrexate and Teriflunomide. Hyper-lipoproteinaemia [5C80] [13]
BMS-201038 DMQTAGO Major Increased risk of hepatotoxicity by the combination of Trimetrexate and BMS-201038. Hyper-lipoproteinaemia [5C80] [14]
Denosumab DMNI0KO Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Denosumab. Low bone mass disorder [FB83] [15]
Calaspargase pegol DMQZBXI Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Calaspargase pegol. Malignant haematopoietic neoplasm [2B33] [16]
Idelalisib DM602WT Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Idelalisib. Mature B-cell leukaemia [2A82] [17]
Tecfidera DM2OVDT Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Tecfidera. Multiple sclerosis [8A40] [18]
Siponimod DM2R86O Major Additive immunosuppressive effects by the combination of Trimetrexate and Siponimod. Multiple sclerosis [8A40] [7]
Fingolimod DM5JVAN Major Additive immunosuppressive effects by the combination of Trimetrexate and Fingolimod. Multiple sclerosis [8A40] [19]
Ocrelizumab DMEZ2KH Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Ocrelizumab. Multiple sclerosis [8A40] [20]
Ozanimod DMT6AM2 Major Additive immunosuppressive effects by the combination of Trimetrexate and Ozanimod. Multiple sclerosis [8A40] [9]
Omacetaxine mepesuccinate DMPU2WX Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Omacetaxine mepesuccinate. Myeloproliferative neoplasm [2A20] [21]
Canakinumab DM8HLO5 Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Canakinumab. Rheumatoid arthritis [FA20] [22]
Rilonacept DMGLUQS Moderate Additive immunosuppressive effects by the combination of Trimetrexate and Rilonacept. Rheumatoid arthritis [FA20] [22]
Golimumab DMHZV7X Major Additive immunosuppressive effects by the combination of Trimetrexate and Golimumab. Rheumatoid arthritis [FA20] [23]
Anthrax vaccine DM9GSWY Moderate Antagonize the effect of Trimetrexate when combined with Anthrax vaccine. Sepsis [1G40-1G41] [24]
Trabectedin DMG3Y89 Moderate Increased risk of hepatotoxicity by the combination of Trimetrexate and Trabectedin. Solid tumour/cancer [2A00-2F9Z] [9]
Valganciclovir DMS2IUH Moderate Additive myelosuppressive effects by the combination of Trimetrexate and Valganciclovir. Virus infection [1A24-1D9Z] [7]
⏷ Show the Full List of 24 DDI Information of This Drug

References

1 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase. Antimicrob Agents Chemother. 2000 Nov;44(11):3092-6.
6 Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 2006 Dec;58(6):826-34.
7 Cerner Multum, Inc. "Australian Product Information.".
8 Product Information. Sirturo (bedaquiline). Janssen Pharmaceuticals, Titusville, NJ.
9 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
10 Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
11 Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
12 Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
13 Product Information. Arava (leflunomide). Hoechst Marion-Roussel Inc, Kansas City, MO.
14 Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
15 Product Information. Prolia (denosumab). Amgen USA, Thousand Oaks, CA.
16 Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
17 Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
18 Product Information. Vumerity (diroximel fumarate). Alkermes, Inc, Cambridge, MA.
19 Product Information. Gilenya (fingolimod). Novartis Pharmaceuticals, East Hanover, NJ.
20 Product Information. Ocrevus (ocrelizumab). Genentech, South San Francisco, CA.
21 Product Information. Synribo (omacetaxine). Teva Pharmaceuticals USA, North Wales, PA.
22 Product Information. Arcalyst (rilonacept). Regeneron Pharmaceuticals Inc, Tarrytown, NY.
23 Product Information. Cimzia (certolizumab). UCB Pharma Inc, Smyrna, GA.
24 CDC. Centers for Disease Control and Prevention/ "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep 42(RR-04) (1993): 1-18. [PMID: 20300058]