U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C19H23N5O3.C2H4O2.H2O
Molecular Weight 447.4849
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIMETREXATE MONOACETATE MONOHYDRATE

SMILES

O.CC(O)=O.COC1=CC(NCC2=C(C)C3=C(N)N=C(N)N=C3C=C2)=CC(OC)=C1OC

InChI

InChIKey=NVDQULLLJIPDRP-UHFFFAOYSA-N
InChI=1S/C19H23N5O3.C2H4O2.H2O/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;1-2(3)4;/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24);1H3,(H,3,4);1H2

HIDE SMILES / InChI

Molecular Formula C19H23N5O3
Molecular Weight 369.4176
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C2H4O2
Molecular Weight 60.052
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Trimetrexate, a second-generation folate antagonist which was used under brand name NEUTREXIN with concurrent leucovorin administration (leucovorin protection) was indicated as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS). Nevertheless, this product was discontinued. In present time, trimetrexate with a different combinations is in the phase II of clinical trial for the treatment the following cancer diseases: pancreatic cancer and colorectal cancer (in combination with fluorouracil and leucovorin) and to treat a refractory acute leukemia in combination with leucovorin. Trimetrexate is a competitive inhibitor of dihydrofolate reductase (DHFR) from bacterial, protozoan, and mammalian sources. DHFR catalyzes the reduction of intracellular dihydrofolate to the active coenzyme tetrahydrofolate. Inhibition of DHFR results in the depletion of this coenzyme, leading directly to interference with thymidylate biosynthesis, as well as inhibition of folate-dependent formyltransferases, and indirectly to inhibition of purine biosynthesis. The result is disruption of DNA, RNA, and protein synthesis, with consequent cell death.

Originator

Curator's Comment: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P00374
Gene ID: 1719.0
Gene Symbol: DHFR
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
NEUTREXIN

Approved Use

Neutrexin (trimetrexate glucuronate for injection) with concurrent leucovorin administration (leucovorin protection) is indicated as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS), who are intolerant of, or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom trimethoprim-sulfamethoxazole is contraindicated. This indication is based on the results of a randomized, controlled double-blind trial comparing Neutrexin with concurrent leucovorin protection (TMTX/LV) to trimethoprim sulfamethoxazole (TMP/SMX) in patients with moderate-to-severe Pneumocystis carinii pneumonia, as well as results of a Treatment IND.

Launch Date

7.5608641E11
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.1 mg/L
30 mg/m² 1 times / day steady-state, intravenous
dose: 30 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered: LEUCOVORIN CALCIUM
TRIMETREXATE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
15.8 mg × h/L
30 mg/m² 1 times / day steady-state, intravenous
dose: 30 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered: LEUCOVORIN CALCIUM
TRIMETREXATE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
30 mg/m² 1 times / day steady-state, intravenous
dose: 30 mg/m²
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered: LEUCOVORIN CALCIUM
TRIMETREXATE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
100 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 100 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / week
Sources:
unhealthy, 49 years
n = 1
Health Status: unhealthy
Condition: pulmonary and pleural metastasis from cutaneous angiosarcoma
Age Group: 49 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5)
Sources:
75 mg/m2 single, intravenous
MTD
Dose: 75 mg/m2
Route: intravenous
Route: single
Dose: 75 mg/m2
Sources:
unhealthy, 63 years
n = 1
Health Status: unhealthy
Condition: adenocarcinoma of the lung
Age Group: 63 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5)
Sources:
10 mg/m2 1 times / day steady, intravenous
MTD
Dose: 10 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 10 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 17
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 17
Sources:
Other AEs: Gastrointestinal signs and symptoms...
Other AEs:
Gastrointestinal signs and symptoms
Sources:
100 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 100 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
DLT: Myelosuppression...
Other AEs: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
Other AEs:
Hematotoxicity (grade 3, 2 patients)
Sources:
110 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 110 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 110 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 3
Sources:
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
130 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 130 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
DLT: Myelosuppression...
Disc. AE: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 2 patients)
Sources:
15 mg/m2 single, intravenous
MTD
Dose: 15 mg/m2
Route: intravenous
Route: single
Dose: 15 mg/m2
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
Other AEs: Gastrointestinal signs and symptoms...
Other AEs:
Gastrointestinal signs and symptoms
Sources:
155 mg/m2 1 times / week multiple, intravenous (max)
MTD
Dose: 155 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 155 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 29
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 29
Sources:
Disc. AE: Hematotoxicity...
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 12 patients)
Sources:
155 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 155 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 155 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 2
Sources:
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
50 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
75 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 75 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 75 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 8
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 8
Sources:
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
90 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 90 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 90 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
DLT: Myelosuppression...
Disc. AE: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Death grade 5
Disc. AE
100 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 100 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / week
Sources:
unhealthy, 49 years
n = 1
Health Status: unhealthy
Condition: pulmonary and pleural metastasis from cutaneous angiosarcoma
Age Group: 49 years
Sex: F
Population Size: 1
Sources:
Death grade 5
Disc. AE
75 mg/m2 single, intravenous
MTD
Dose: 75 mg/m2
Route: intravenous
Route: single
Dose: 75 mg/m2
Sources:
unhealthy, 63 years
n = 1
Health Status: unhealthy
Condition: adenocarcinoma of the lung
Age Group: 63 years
Sex: F
Population Size: 1
Sources:
Gastrointestinal signs and symptoms
10 mg/m2 1 times / day steady, intravenous
MTD
Dose: 10 mg/m2, 1 times / day
Route: intravenous
Route: steady
Dose: 10 mg/m2, 1 times / day
Sources:
unhealthy, adult
n = 17
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 17
Sources:
Myelosuppression DLT
100 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 100 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
Hematotoxicity grade 3, 2 patients
100 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 100 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 100 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
Myelosuppression DLT
110 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 110 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 110 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 3
Sources:
Myelosuppression DLT
130 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 130 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
Hematotoxicity grade 2, 2 patients
Disc. AE
130 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 130 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 130 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
Gastrointestinal signs and symptoms
15 mg/m2 single, intravenous
MTD
Dose: 15 mg/m2
Route: intravenous
Route: single
Dose: 15 mg/m2
Sources:
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
Hematotoxicity grade 2, 12 patients
Disc. AE
155 mg/m2 1 times / week multiple, intravenous (max)
MTD
Dose: 155 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 155 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 29
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 29
Sources:
Myelosuppression DLT
155 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 155 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 155 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 2
Sources:
Myelosuppression DLT
50 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 50 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 50 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
Myelosuppression DLT
75 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 75 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 75 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 8
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 8
Sources:
Myelosuppression DLT
90 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 90 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 90 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
Hematotoxicity grade 2, 1 patient
Disc. AE
90 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 90 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 90 mg/m2, 1 times / week
Sources:
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
likely (co-administration study)
Comment: concomitant administration of SPORANOX (itraconazole) and trimetrexate may inhibit the metabolism of trimetrexate
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase inhibitor, in rat and dog.
1990 Nov-Dec
Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.
1991 Jul
Low-dose trimetrexate glucuronate and protracted 5-fluorouracil infusion in previously untreated patients with advanced pancreatic cancer.
2002 Apr
Gateways to clinical trials.
2002 Dec
Role of the E45K-reduced folate carrier gene mutation in methotrexate resistance in human leukemia cells.
2002 Dec
Methylthioadenosine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells.
2002 Jan-Feb
Trimetrexate in relapsed T-cell lymphoma with skin involvement.
2002 Jun 15
Phase II evaluation of oral trimetrexate in mixed mesodermal tumors of the uterus: a gynecologic oncology group study.
2002 May
Does leucovorin alter the intratumoral pharmacokinetics of 5-fluorouracil (5-FU)? A Southwest Oncology Group study.
2002 Nov
Resistance to multiple novel antifolates is mediated via defective drug transport resulting from clustered mutations in the reduced folate carrier gene in human leukaemia cell lines.
2002 Nov 1
Analysis of quinazoline and pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolates in complex with NADP+ and Pneumocystis carinii dihydrofolate reductase.
2002 Sep
The murine-reduced folate carrier gene can act as a selectable marker and a suicide gene in hematopoietic cells in vivo.
2002 Sep 20
Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells.
2002 Sep-Oct
Decreased expression of the reduced folate carrier and folypolyglutamate synthetase is the basis for acquired resistance to the pemetrexed antifolate (LY231514) in an L1210 murine leukemia cell line.
2003 Apr 1
Increased resistance to nitrogen mustards and antifolates following in vitro selection of murine fibroblasts and primary hematopoietic cells transduced with a bicistronic retroviral vector expressing the rat glutathione S-transferase A3 and a mutant dihydrofolate reductase.
2003 Aug
Thymidine and hypoxanthine protection patterns of the folic acid-enhanced synergies for combinations of trimetrexate plus a polyglutamylatable inhibitor of purine or thymidylate synthesis against human ileocecal HCT-8 cells.
2003 Aug
Large diversity in transport-mediated methotrexate resistance in human leukemia cell line CCRF-CEM established in a high concentration of leucovorin.
2003 Feb
Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase.
2003 Mar 15
Imaging of dihydrofolate reductase fusion gene expression in xenografts of human liver metastases of colorectal cancer in living rats.
2003 Sep
Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry.
2004 Apr
Transient in vivo selection of transduced peripheral blood cells using antifolate drug selection in rhesus macaques that received transplants with hematopoietic stem cells expressing dihydrofolate reductase vectors.
2004 Feb 1
p14ARF expression increases dihydrofolate reductase degradation and paradoxically results in resistance to folate antagonists in cells with nonfunctional p53.
2004 Jun 15
Synthesis of 2,4-diamino-6-[2'-O-(omega-carboxyalkyl)oxydibenz[b,f]azepin-5-yl]methylpteridines as potent and selective inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductase.
2004 May 6
Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.
2004 Oct
Tolerance by selective in vivo expansion of foreign major histocompatibility complex-transduced autologous bone marrow.
2005 Aug 15
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Highly efficient transduction of repopulating bone marrow cells using rapidly concentrated polymer-complexed retrovirus.
2005 May 13
A phase I/II study of trimetrexate and capecitabine in patients with advanced refractory colorectal cancer.
2005 Oct
Towards species-specific antifolates.
2006
Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates.
2006 Dec
Commentary: a case for minimizing folate supplementation in clinical regimens with pemetrexed based on the marked sensitivity of the drug to folate availability.
2007 Jul
Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.
2007 May-Jun
Effects of folate and folylpolyglutamyl synthase modulation on chemosensitivity of breast cancer cells.
2007 Nov
Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy.
2008 Aug 1
Radiation recall dermatitis: case report and review of the literature.
2008 Jan
Chemical and genetic validation of dihydrofolate reductase-thymidylate synthase as a drug target in African trypanosomes.
2008 Jul
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.
2008 May
Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy.
2008 Sep
A mapping of drug space from the viewpoint of small molecule metabolism.
2009 Aug
Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: a tri-centre cohort study.
2009 Dec
Interpretable correlation descriptors for quantitative structure-activity relationships.
2009 Dec 24
Structures of dihydrofolate reductase-thymidylate synthase of Trypanosoma cruzi in the folate-free state and in complex with two antifolate drugs, trimetrexate and methotrexate.
2009 Jul
Trimetrexate and folinic acid: a valuable salvage option for Pneumocystis jirovecii pneumonia.
2009 Jun 19
Radiation recall with anticancer agents.
2010
S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.
2010 Apr
High-resolution structures of Trypanosoma brucei pteridine reductase ligand complexes inform on the placement of new molecular entities in the active site of a potential drug target.
2010 Dec
Applying Emax model and bivariate thin plate splines to assess drug interactions.
2010 Jan 1
Comparison of methods for statistical analysis of combination studies.
2010 Jan 1
Comparison of methods for evaluating drug-drug interaction.
2010 Jan 1
Synthesis and biological evaluation of biguanide and dihydrotriazine derivatives as potential inhibitors of dihydrofolate reductase of opportunistic microorganisms.
2010 Jun
Patents

Sample Use Guides

Neutrexin (trimetrexate glucuronate for injection) is administered at a dose of 45 mg/m2 once daily by intravenous infusion over 60 minutes. Leucovorin must be administered daily during treatment with Neutrexin and for 72 hours past the last dose of Neutrexin. Leucovorin may be administered intravenously at a dose of 20 mg/m2 over 5 to 10 minutes every 6 hours for a total daily dose of 80 mg/m2, or orally as 4 doses of 20 mg/m2 spaced equally throughout the day. The oral dose should be rounded up to the next higher 25 mg increment. The recommended course of therapy is 21 days of Neutrexin and 24 days of leucovorin.
Route of Administration: Intravenous
In Vitro Use Guide
Carboxypeptidase G2 (CPG2), an enzyme produced by Pseudomonas strain RS-16, hydrolyzes the glutamate residue from methotrexate and other folates. The possibility of enhancing trimetrexate cytotoxicity by CPG2 induced folate depletion was investigated in vitro in a human leukemia cell line, CCRF-CEM, and in three sublines of these cells each with a different methotrexate resistance phenotype. Trimetrexate alone was cytotoxic against the parent and all the resistant cell lines with the drug concentrations required to decrease the cell count to 50% of control in the nanomolar range (1.4, 1.6, 1.5, and 0.7 nM in CCRF-CEM, CCRF-CEM/E, CCRF-CEM/P, and CCRF-CEM/T, respectively) following 5 days of exposure.
Substance Class Chemical
Created
by admin
on Wed Jul 05 23:37:53 UTC 2023
Edited
by admin
on Wed Jul 05 23:37:53 UTC 2023
Record UNII
202B4JX1JJ
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMETREXATE MONOACETATE MONOHYDRATE
MI  
Common Name English
TRIMETREXATE MONOACETATE MONOHYDRATE [MI]
Common Name English
2,4-QUINAZOLINEDIAMINE, 5-METHYL-6-(((3,4,5-TRIMETHOXYPHENYL)AMINO)METHYL)-, MONOACETATE, MONOHYDRATE
Systematic Name English
TRIMETREXATE ACETATE MONOHYDRATE
Common Name English
2,4-QUINAZOLINEDIAMINE, 5-METHYL-6-(((3,4,5-TRIMETHOXYPHENYL)AMINO)METHYL)-, ACETATE, HYDRATE (1:1:1)
Systematic Name English
Code System Code Type Description
MERCK INDEX
M11163
Created by admin on Wed Jul 05 23:37:53 UTC 2023 , Edited by admin on Wed Jul 05 23:37:53 UTC 2023
PRIMARY Merck Index
FDA UNII
202B4JX1JJ
Created by admin on Wed Jul 05 23:37:53 UTC 2023 , Edited by admin on Wed Jul 05 23:37:53 UTC 2023
PRIMARY
CAS
117381-09-6
Created by admin on Wed Jul 05 23:37:53 UTC 2023 , Edited by admin on Wed Jul 05 23:37:53 UTC 2023
PRIMARY
PUBCHEM
21186988
Created by admin on Wed Jul 05 23:37:53 UTC 2023 , Edited by admin on Wed Jul 05 23:37:53 UTC 2023
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY