trimetrexate Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
folic acid analogues 2757 52128-35-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • trimetrexate hydrate
  • trimetrexate glucuronate
  • trimetrexate
  • CI-898
  • JB-11
A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.
  • Molecular weight: 369.43
  • Formula: C19H23N5O3
  • CLOGP: 1.84
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 117.54
  • ALOGS: -4.08
  • ROTB: 6

  • Status: OFM

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
85 mg P

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 50 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 20 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 3.30 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 45 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.77 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.77 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 17 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 17, 1993 FDA

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

Pharmacologic Action:

SourceCodeDescription
ATC P01AX07 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
AGENTS AGAINST AMOEBIASIS AND OTHER PROTOZOAL DISEASES
Other agents against amoebiasis and other protozoal diseases
MeSH PA D000963 Antimetabolites
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000935 Antifungal Agents
MeSH PA D000964 Antimetabolites, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D005493 Folic Acid Antagonists
MeSH PA D009676 Noxae
CHEBI has role CHEBI:86327 anti-fungal medications

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Pneumocystosis jiroveci pneumonia indication 415125002 DOID:11339
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.3 Basic
pKa2 2.49 Basic
pKa3 0.09 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dihydrofolate reductase Enzyme Ki 8.85 CHEMBL
Folylpolyglutamate synthase, mitochondrial Enzyme WOMBAT-PK
Dihydrofolate reductase Enzyme INHIBITOR Ki 9.15 CHEMBL CHEMBL
Dihydrofolate reductase Enzyme IC50 7.57 CHEMBL
Dihydrofolate reductase Enzyme IC50 8 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 8.29 CHEMBL
Dihydrofolate reductase Enzyme Ki 10.22 CHEMBL
Dihydrofolate reductase Enzyme IC50 7.38 CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme Ki 8.18 CHEMBL
Dihydrofolate reductase Enzyme Ki 8.72 CHEMBL
Dihydrofolate reductase Enzyme IC50 8.52 CHEMBL
Dihydrofolate reductase Enzyme IC50 8.82 CHEMBL
Dihydrofolate reductase Unclassified IC50 8.15 CHEMBL

External reference:

IDSource
4023899 VUID
N0000171585 NUI
D06238 KEGG_DRUG
82952-64-5 SECONDARY_CAS_RN
4020845 VANDF
4023899 VANDF
C0701241 UMLSCUI
CHEBI:9737 CHEBI
TMQ PDB_CHEM_ID
CHEMBL119 ChEMBL_ID
CHEMBL2218878 ChEMBL_ID
D016597 MESH_DESCRIPTOR_UI
5583 PUBCHEM_CID
C056321 MESH_SUPPLEMENTAL_RECORD_UI
5103 INN_ID
DB01157 DRUGBANK_ID
UPN4ITI8T4 UNII
7613 IUPHAR_LIGAND_ID
38725 RXNORM
5635 MMSL
d03169 MMSL
004411 NDDF
004412 NDDF
116544008 SNOMEDCT_US
372899008 SNOMEDCT_US
91339009 SNOMEDCT_US

Pharmaceutical products:

None