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

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H23N5O3.C6H10O7
Molecular Weight 563.557
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRIMETREXATE GLUCURONATE

SMILES

O[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O.COC1=CC(NCC2=C(C)C3=C(N)N=C(N)N=C3C=C2)=CC(OC)=C1OC

InChI

InChIKey=ZCJXQWYMBJYJNB-LRDBBFHQSA-N
InChI=1S/C19H23N5O3.C6H10O7/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;7-1-2(8)3(9)4(10)5(11)6(12)13/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24);1-5,8-11H,(H,12,13)/t;2-,3+,4-,5-/m.0/s1

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 C6H10O7
Molecular Weight 194.1394
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

Pfizer
407
Curator's Comment: # Pfizer

Approval Year

1993
137
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8228
Dihydrofolate reductase
56
Target ID: P00374
Gene ID: 1719.0
Gene Symbol: DHFR
Target Organism: Homo sapiens (Human)
Inhibitor
8228
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Approved
8360
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
Phase II
1144
Unknown

Approved Use

Unknown
Primary
Phase II
1144
Unknown

Approved Use

Unknown
Primary
Phase II
1144
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.1 mg/L
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/7789290
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
LEUCOVORIN CALCIUM
 TRIMETREXATE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
15.8 mg × h/L
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/7789290
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
LEUCOVORIN CALCIUM
 TRIMETREXATE plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
REVIEW
https://www.ncbi.nlm.nih.gov/pubmed/7789290
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
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
75 mg/m2 single, intravenous
MTD
Dose: 75 mg/m2
Route: intravenous
Route: single
Dose: 75 mg/m2
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, 63 years
n = 1
Health Status: unhealthy
Condition: adenocarcinoma of the lung
Age Group: 63 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Disc. AE: Death...
AEs leading to
discontinuation/dose reduction:
Death (grade 5)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/1831340/
unhealthy, adult
n = 17
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
Other AEs: Gastrointestinal signs and symptoms...
Other AEs:
Gastrointestinal signs and symptoms
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Other AEs: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
Other AEs:
Hematotoxicity (grade 3, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Disc. AE: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 2 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
15 mg/m2 single, intravenous
MTD
Dose: 15 mg/m2
Route: intravenous
Route: single
Dose: 15 mg/m2
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
Other AEs: Gastrointestinal signs and symptoms...
Other AEs:
Gastrointestinal signs and symptoms
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 29
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Disc. AE: Hematotoxicity...
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 12 patients)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 8
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Dose limiting toxicities:
Myelosuppression
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
DLT: Myelosuppression...
Disc. AE: Hematotoxicity...
Dose limiting toxicities:
Myelosuppression
AEs leading to
discontinuation/dose reduction:
Hematotoxicity (grade 2, 1 patient)
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Death grade 5
Disc. AE
75 mg/m2 single, intravenous
MTD
Dose: 75 mg/m2
Route: intravenous
Route: single
Dose: 75 mg/m2
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, 63 years
n = 1
Health Status: unhealthy
Condition: adenocarcinoma of the lung
Age Group: 63 years
Sex: F
Population Size: 1
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/1831340/
unhealthy, adult
n = 17
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 17
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 4
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 4
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 3
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 3
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Gastrointestinal signs and symptoms
15 mg/m2 single, intravenous
MTD
Dose: 15 mg/m2
Route: intravenous
Route: single
Dose: 15 mg/m2
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
unhealthy, adult
n = 18
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 18
Sources:
https://pubmed.ncbi.nlm.nih.gov/1831340/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 29
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 2
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 7
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 7
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 8
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
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:
https://pubmed.ncbi.nlm.nih.gov/2953412/
unhealthy, adult
n = 6
Health Status: unhealthy
Condition: solid cancer
Age Group: adult
Sex: unknown
Population Size: 6
Sources:
https://pubmed.ncbi.nlm.nih.gov/2953412/
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer
CYP 450
31
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP 450
31
 yes
likely (co-administration study)
Comment: concomitant administration of SPORANOX (itraconazole) and trimetrexate may inhibit the metabolism of trimetrexate
Sourcing

Sourcing

Vendor/AggregatorIDURL
001 Chemical
DY558210
https://www.001chemical.com/chem/52128-35-5
AA Blocks
AA00DB6L
https://www.aablocks.com/goods/Goods/detail?id=AA00DB6L
Achemtek
0101-002318
http://www.achemtek.com/52128-35-5
Adooq BioScience
A12796
https://www.adooq.com/trimetrexate.html
Ambinter
Amb22731961
http://www.ambinter.com/reference/22731961
Angel Pharmatech
AG302845
http://www.angelpharmatech.com/52128-35-5.html
BLD Pharm
BD155583
http://www.bldpharm.com/products/52128-35-5.html
BioChemPartner
BCP15515
http://www.biochempartner.com/52128-35-5-BCP15515
CSNpharm
CSN12149
https://www.csnpharm.com/products/trimetrexate.html
Chem Scene
CS-4063
http://www.chemscene.com/52128-35-5.html
Chemspace
CSSB00020617805
https://chem-space.com/CSSB00020617805
DC Chemicals
DC23932
http://www.dcchemicals.com/product_show-DC23932.html
Finetech
FT-0649497
http://www.finetechnology-ind.com/prod/detail/pub/52128-35-5.html
Lab Network
LN01342098
https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342098
MedChem Express
HY-10373
https://www.medchemexpress.com/Trimetrexate.html
Molcore
MC558210
https://www.molcore.com/product/52128-35-5
Parchem
30218
http://www.parchem.com/chemical-supplier-distributor/Trimetrexate-020218.aspx
Smolecule
S545904
http://www.smolecule.com/products/s545904
Smolecule
S772620
https://www.smolecule.com/products/s772620
THE BioTek
bt-287020
https://www.thebiotek.com/product/inhibitors/bt-287020
eNovation Chemicals
D673579
https://www.enovationchem.com/ProductDetails.asp?ProductID=D673579
PubMed

PubMed

TitleDatePubMed
Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase inhibitor, in rat and dog.
1990 Nov-Dec
Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase.
2000 Nov
Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii.
2001 Jul 19
RD114-pseudotyped oncoretroviral vectors. Biological and physical properties.
2001 Jun
Gateways to clinical trials.
2002 Dec
Role of the E45K-reduced folate carrier gene mutation in methotrexate resistance in human leukemia cells.
2002 Dec
A double-blind placebo-controlled randomized phase III trial of 5-fluorouracil and leucovorin, plus or minus trimetrexate, in previously untreated patients with advanced colorectal cancer.
2002 Jan
Methylthioadenosine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells.
2002 Jan-Feb
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
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
Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6-substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors.
2004 Jul 1
Design, synthesis, and computational affinity prediction of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii.
2004 May
Superior depletion of alloreactive T cells from peripheral blood stem cell and umbilical cord blood grafts by the combined use of trimetrexate and interleukin-2 immunotoxin.
2004 Nov
Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.
2004 Oct
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
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
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.
2008 May
Interpretable correlation descriptors for quantitative structure-activity relationships.
2009 Dec 24
Radiation recall with anticancer agents.
2010
Academia-pharma intersect: providing a broader perspective on drug development synergies between academia and industry.
2010
The immunobiology of cord blood transplantation.
2010 Dec
Gateways to clinical trials.
2010 Dec
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
A review of synergy concepts of nonlinear blending and dose-reduction profiles.
2010 Jan 1
Emax model and interaction index for assessing drug interaction in combination studies.
2010 Jan 1
Applying Emax model and bivariate thin plate splines to assess drug interactions.
2010 Jan 1
Application and review of the separate ray model to investigate interaction effects.
2010 Jan 1
Efficient experimental design and nonparametric modeling of drug interaction.
2010 Jan 1
Comparison of methods for statistical analysis of combination studies.
2010 Jan 1
Synthesis and biological evaluation of biguanide and dihydrotriazine derivatives as potential inhibitors of dihydrofolate reductase of opportunistic microorganisms.
2010 Jun
Anticancer agents against malaria: time to revisit?
2010 Mar
Cancer chemotherapy: targeting folic acid synthesis.
2010 Nov 19
Patents

Patents

05534518
6
JP2005520795A
24
JP3775780B2
13
JP4787165B2
100

Sample Use Guides

In Vivo Use Guide
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 23:00:45 UTC 2023
Edited
by admin
on Wed Jul 05 23:00:45 UTC 2023
Record UNII
L137U4A79K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRIMETREXATE GLUCURONATE
MART.   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN  
Official Name English
2,4-QUINAZOLINEDIAMINE, 5-METHYL-6-(((3,4,5-TRIMETHOXYPHENYL)AMINO)METHYL)-, MONO-D-GLUCURONATE
Common Name English
TRIMETREXATE GLUCURONATE [MART.]
Common Name English
Trimetrexate glucuronate [WHO-DD]
Common Name English
TRIMETREXATE GLUCURONATE [ORANGE BOOK]
Common Name English
TRIMETREXATE D-GLUCURONATE
MI  
Common Name English
CI-898
Code English
NEUTREXIN
Brand Name English
D-GLUCURONIC ACID, COMPD. WITH 5-METHYL-6-(((3,4,5-TRIMETHOXYPHENYL)AMINO)METHYL)-2,4-QUINAZOLINEDIAMINE (1:1)
Systematic Name English
NSC-352122
Code English
2,4-DIAMINO-5-METHYL-6-((3,4,5-TRIMETHOXYANILINO)METHYL)QUINAZOLINE MONO-D-GLUCURONATE
Common Name English
TRIMETREXATE GLUCURONATE [VANDF]
Common Name English
TRIMETREXATE GLUCURONATE [USAN]
Common Name English
TRIMETREXATE D-GLUCURONATE [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 14286
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
FDA ORPHAN DRUG 14686
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
FDA ORPHAN DRUG 8385
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
NCI_THESAURUS C2153
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID90273968
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
PUBCHEM
54949
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
NCI_THESAURUS
C1265
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
RXCUI
38725
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY RxNorm
NSC
352122
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
CAS
82952-64-5
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
MERCK INDEX
M11163
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY Merck Index
EVMPD
SUB04976MIG
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
SMS_ID
100000084647
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
FDA UNII
L137U4A79K
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
DRUG BANK
DBSALT002433
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
ChEMBL
CHEMBL119
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
MESH
C056321
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
USAN
AA-34
Created by admin on Wed Jul 05 23:00:45 UTC 2023 , Edited by admin on Wed Jul 05 23:00:45 UTC 2023
PRIMARY
Related Record Type Details
Structure of TRIMETREXATE
PARENT -> SALT/SOLVATE
Related Record Type Details
Structure of TRIMETREXATE
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