Details
| Stereochemistry | EPIMERIC |
| Molecular Formula | C22H25N7O5.H2O |
| Molecular Weight | 485.4931 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.CCC(CC1=NC2=C(N=C1)N=C(N)N=C2N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
InChI
InChIKey=ANBVTUQPYAYQBF-XEKVDKDVSA-N
InChI=1S/C22H25N7O5.H2O/c1-2-11(9-14-10-25-19-17(26-14)18(23)28-22(24)29-19)12-3-5-13(6-4-12)20(32)27-15(21(33)34)7-8-16(30)31;/h3-6,10-11,15H,2,7-9H2,1H3,(H,27,32)(H,30,31)(H,33,34)(H4,23,24,25,28,29);1H2/t11?,15-;/m0./s1
Edatrexate (10-ethyl-10-deazaaminopterin or 10-EDAM) is an analog of methotrexate with improved pre-clinical antitumor activity, more selective cellular uptake, and with the more extensive formation of intracellular polyglutamate metabolites. This drug is a new dihydrofolate reductase inhibitor, which was studied in phase II clinical trial for the patients with different cancers. The studies were discontinued, for example, in advanced renal cell carcinoma edatrexate in the investigated dose and schedule had minimal activity and was toxic. In case of non-small-cell lung cancer, the dosing schedule of edatrexate did not appear to be improved compared to other chemotherapeutic regimens. In addition, edatrexate was involved in the experiment for the treatemnt of rheumatoid arthritis, but this study was also discontinued.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: P00374 Gene ID: 1719.0 Gene Symbol: DHFR Target Organism: Homo sapiens (Human) |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Palliative | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
13272 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9816135 |
1080 mg/m² 1 times / week multiple, intravenous dose: 1080 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: LEUCOVORIN |
EDATREXATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
39702 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9816135 |
1080 mg/m² 1 times / week multiple, intravenous dose: 1080 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: LEUCOVORIN |
EDATREXATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9816135 |
1080 mg/m² 1 times / week multiple, intravenous dose: 1080 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered: LEUCOVORIN |
EDATREXATE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
400 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 400 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 400 mg/m2, 1 times / 3 weeks Co-administed with:: Paclitaxel(175 mg/m2 as a 3-h infusion) Sources: Page: p.277 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.277 |
DLT: Stomatitis, Diarrhea... Dose limiting toxicities: Stomatitis (grade 4, 66.7%) Sources: Page: p.277Diarrhea (grade 3, 33.3%) |
350 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 350 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 350 mg/m2, 1 times / 3 weeks Co-administed with:: Paclitaxel(175 mg/m2 as a 3-h infusion) Sources: Page: p.277 |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 5 Sources: Page: p.277 |
|
270 mg/m2 1 times / 2 weeks multiple, intravenous Studied dose Dose: 270 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 270 mg/m2, 1 times / 2 weeks Sources: Page: p.476 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.476 |
|
3750 mg/m2 1 times / week multiple, intravenous MTD Dose: 3750 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3750 mg/m2, 1 times / week Co-administed with:: leucovorin(10 mg/m2, every 6 h for 10 doses) Sources: Page: p.1822 |
unhealthy n = 3 Health Status: unhealthy Condition: cancer Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1822 |
Disc. AE: Leukoencephalopathy... AEs leading to discontinuation/dose reduction: Leukoencephalopathy (33.3%) Sources: Page: p.1822 |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Diarrhea | grade 3, 33.3% DLT, Disc. AE |
400 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 400 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 400 mg/m2, 1 times / 3 weeks Co-administed with:: Paclitaxel(175 mg/m2 as a 3-h infusion) Sources: Page: p.277 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.277 |
| Stomatitis | grade 4, 66.7% DLT, Disc. AE |
400 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 400 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 400 mg/m2, 1 times / 3 weeks Co-administed with:: Paclitaxel(175 mg/m2 as a 3-h infusion) Sources: Page: p.277 |
unhealthy, ADULT n = 3 Health Status: unhealthy Condition: breast cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.277 |
| Leukoencephalopathy | 33.3% Disc. AE |
3750 mg/m2 1 times / week multiple, intravenous MTD Dose: 3750 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 3750 mg/m2, 1 times / week Co-administed with:: leucovorin(10 mg/m2, every 6 h for 10 doses) Sources: Page: p.1822 |
unhealthy n = 3 Health Status: unhealthy Condition: cancer Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: Page: p.1822 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Synthesis and antifolate evaluation of 10-ethyl-5-methyl-5,10- dideazaaminopterin and an alternative synthesis of 10-ethyl-10- deazaaminopterin (edatrexate). | 1992 Aug 7 |
|
| Schedule-dependent synergism of edatrexate and cisplatin in combination in the A549 lung-cancer cell line as assessed by median-effect analysis. | 1993 |
|
| Schedule-dependent synergism of taxol or taxotere with edatrexate against human breast cancer cells in vitro. | 1996 |
|
| Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study. | 1997 |
|
| Phase I trial of edatrexate plus carboplatin in advanced solid tumors: amelioration of dose-limiting mucositis by ice chip cryotherapy. | 1998 |
|
| The role of circulating immune complexes and biocompatibility of staphylococcal protein A immunoadsorption in mitomycin C-induced hemolytic uremic syndrome. | 2004 Oct |
Patents
Sample Use Guides
cancer; treatment consisted of edatrexate 80 mg/m2 (50% dose on day 8) intravenously weekly for 5 weeks, then every other week, and carboplatin 350 mg/m2 every 28 days
rheumatoid arthritis: hairless mouse skin: transdermal: 85 micrograms/cm2/hr
Route of Administration:
Other
It was evaluated the ability of edatrexate to modulate the intrinsic resistance of the lung adenocarcinoma A549 cell line to carboplatin. Concentration effects, exposure time and schedule dependence were assessed. Modulation of resistance was observed with edatrexate treatment (0.2 microM for 1 h) prior to carboplatin. The concentrations of carboplatin to achieve IC50 at the 1-, 3-, and 24-h IC50 were decreased by a mean of 16.8 times (12.2-22.2) with edatrexate preexposure. In contrast, there was little modulation observed of carboplatin resistance when carboplatin was administered prior to edatrexate. In addition, schedule dependency experiments were performed using the method described by Chou and Talalay, in which the ratio of carboplatin to edatrexate was constant or nonconstant, and both the potency of effects and the shapes of the concentration-effect curves were taken into account in a computerized analysis.
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5KMD2L467S
Created by
admin on Sat Dec 16 19:57:47 GMT 2023 , Edited by admin on Sat Dec 16 19:57:47 GMT 2023
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PRIMARY |
ACTIVE MOIETY
SUBSTANCE RECORD
