TRIMETREXATE GLUCURONATE

US Previously Marketed

First approved in 1993

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 Search

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

Description
Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad0f8925-f817-4460-aa6b-172a043a440b | https://www.ncbi.nlm.nih.gov/pubmed/15361639 | https://www.ncbi.nlm.nih.gov/pubmed/16199980

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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dihydrofolate reductase 57 Target ID: CHEMBL1926 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11448221	Inhibitor 8297
Dihydrofolate reductase 57 Target ID: P00374 Gene ID: 1719.0 Gene Symbol: DHFR Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12649191	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Pneumocystis carinii pneumonia 4 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad0f8925-f817-4460-aa6b-172a043a440b	Curative	Approved 8429	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 1993
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15361639	Primary	Phase II 1132	Unknown Approved Use Unknown
Colorectal cancer 101 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16199980	Primary	Phase II 1132	Unknown Approved Use Unknown
Refractory acute leukemia 4 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7834472	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP 450 31

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 450 31	substrate 3367 Sources: https://link.springer.com/article/10.2165/00003495-199549040-00007; https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020083s048s049s050lbl.pdf#page=18	yes		likely (co-administration study) Comment: concomitant administration of SPORANOX (itraconazole) and trimetrexate may inhibit the metabolism of trimetrexate Sources: https://link.springer.com/article/10.2165/00003495-199549040-00007; https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020083s048s049s050lbl.pdf#page=18

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs.	1991 Jul	1929292
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Gateways to clinical trials.	2002 Dec	12616965
Does leucovorin alter the intratumoral pharmacokinetics of 5-fluorouracil (5-FU)? A Southwest Oncology Group study.	2002 Nov	12448653
Phase II clinical trial of 5-fluorouracil, trimetrexate, and leucovorin (NFL) in patients with advanced pancreatic cancer.	2003	15361639
Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductase.	2003 Apr	12657784
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	12663051
Quinoxaline chemistry. Part 15. 4-[2-Quinoxalylmethylenimino]-benzoylglutamates and -benzoates, 4-[2-quinoxalylmethyl-N-methylamino]-benzoylglutamates as analogues of classical antifolate agents. Synthesis, elucidation of structures and in vitro evaluation of antifolate and anticancer activities.	2003 Jan	12595037
Chemotherapy for malignant pleural mesothelioma: past results and recent developments.	2003 Jan 27	12610498
Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia.	2003 Jul	12890330
Dihydrofolate reductase mutant with exceptional resistance to methotrexate but not to trimetrexate.	2003 Jul 3	12825924
The role of multidrug resistance proteins MRP1, MRP2 and MRP3 in cellular folate homeostasis.	2003 Mar 1	12628490
Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase.	2003 Mar 15	12649191
A new nonlinear mixture response surface paradigm for the study of synergism: a three drug example.	2003 Oct	14529372
Double modulation of 5-fluorouracil by trimetrexate and leucovorin in patients with advanced colorectal carcinoma.	2004 Apr	15057154
Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry.	2004 Apr	15039552
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	12920024
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	15214795
p14ARF expression increases dihydrofolate reductase degradation and paradoxically results in resistance to folate antagonists in cells with nonfunctional p53.	2004 Jun 15	15205349
19F-magnetic resonance spectroscopy in patients with liver metastases of colorectal cancer treated with 5-fluorouracil.	2004 Mar	15014355
Design, synthesis, and computational affinity prediction of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii.	2004 May	15113582
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	15115391
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	15505608
Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance.	2004 Oct	15504256
Characterization of a folate transporter in HeLa cells with a low pH optimum and high affinity for pemetrexed distinct from the reduced folate carrier.	2004 Sep 15	15448015
Tolerance by selective in vivo expansion of foreign major histocompatibility complex-transduced autologous bone marrow.	2005 Aug 15	16082332
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Highly efficient transduction of repopulating bone marrow cells using rapidly concentrated polymer-complexed retrovirus.	2005 May 13	15809063
A phase I/II study of trimetrexate and capecitabine in patients with advanced refractory colorectal cancer.	2005 Oct	16199980
Towards species-specific antifolates.	2006	16475929
Complete regression of large solid tumors using engineered drug-resistant hematopoietic cells and anti-CD137 immunotherapy.	2006 Aug	16942440
Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates.	2006 Dec	16612649
A phase II trial of S-1 monotherapy in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens.	2006 Dec 18	17106441
The inverse relationship between reduced folate carrier function and pemetrexed activity in a human colon cancer cell line.	2006 Feb	16505119
The protection against trimetrexate cytotoxicity in human bone marrow by sequence-dependent administration of raloxifene, 5-fluorouracil/trimetrexate.	2006 Nov-Dec	17201145
Raloxifene and selective cell cycle specific agents: a case for the inclusion of raloxifene in current breast cancer treatment therapies.	2007 May-Jun	17595753
Epigenetic mechanisms involved in differential MDR1 mRNA expression between gastric and colon cancer cell lines and rationales for clinical chemotherapy.	2008 Aug 1	18673531
Impairments in antifolate transport are common in retinoblastoma tumor samples.	2008 Mar	17554792
Effect of folate derivatives on the activity of antifolate drugs used against malaria and cancer.	2008 May	18259776
Current status and perspectives regarding the treatment of osteo-sarcoma: chemotherapy.	2008 Sep	18782081
A mapping of drug space from the viewpoint of small molecule metabolism.	2009 Aug	19701464
Clinical efficacy of first- and second-line treatments for HIV-associated Pneumocystis jirovecii pneumonia: a tri-centre cohort study.	2009 Dec	19858161
Radiation recall with anticancer agents.	2010	21045191
The immunobiology of cord blood transplantation.	2010 Dec	21253423
Gateways to clinical trials.	2010 Dec	21225012
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	21123874
Applying Emax model and bivariate thin plate splines to assess drug interactions.	2010 Jan 1	20036878
Comparison of methods for statistical analysis of combination studies.	2010 Jan 1	20036875
Anticancer agents against malaria: time to revisit?	2010 Mar	20056487
Cancer chemotherapy: targeting folic acid synthesis.	2010 Nov 19	21301589

Patents

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.

Name

Type

Language

TRIMETREXATE GLUCURONATE

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

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