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Details

Stereochemistry UNKNOWN
Molecular Formula C22H25N7O5
Molecular Weight 467.4778
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EDATREXATE

SMILES

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=FSIRXIHZBIXHKT-MHTVFEQDSA-N
InChI=1S/C22H25N7O5/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)/t11?,15-/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H25N7O5
Molecular Weight 467.4778
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 1 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Targets

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

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
13272 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
39702 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
4.1 h
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

Doses

DosePopulationAdverse 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%)
Diarrhea (grade 3, 33.3%)
Sources: Page: p.277
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

AEs

AESignificanceDosePopulation
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

PubMed

TitleDatePubMed
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
In Vitro Use Guide
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 16:05:07 UTC 2023
Edited
by admin
on Sat Dec 16 16:05:07 UTC 2023
Record UNII
JT4X6Z1HRR
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
EDATREXATE
INN   MART.   MI   USAN  
INN   USAN  
Official Name English
EDATREXATE [MI]
Common Name English
NSC-626715
Code English
EDATREXATE [USAN]
Common Name English
EDATREXATE [MART.]
Common Name English
CGP 30694
Code English
edatrexate [INN]
Common Name English
TCMDC-137768
Code English
L-GLUTAMIC ACID, N-(4-(1-((2,4-DIAMINO-6-PTERIDINYL)METHYL)PROPYL)BENZOYL)-
Common Name English
Edatrexate [WHO-DD]
Common Name English
GNF-PF-63
Code English
CGP-30694
Code English
Classification Tree Code System Code
NCI_THESAURUS C511
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
NCI_THESAURUS C2153
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
Code System Code Type Description
DRUG CENTRAL
986
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
MERCK INDEX
m4824
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY Merck Index
ChEMBL
CHEMBL296373
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
EVMPD
SUB06454MIG
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
PUBCHEM
6917908
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
CAS
80576-83-6
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
SMS_ID
100000080509
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
EPA CompTox
DTXSID901318475
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
INN
6471
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
NSC
626715
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
USAN
CC-35
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
FDA UNII
JT4X6Z1HRR
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
NCI_THESAURUS
C958
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
MESH
C040210
Created by admin on Sat Dec 16 16:05:08 UTC 2023 , Edited by admin on Sat Dec 16 16:05:08 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
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ACTIVE MOIETY