EDATREXATE MONOHYDRATE

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

Structure Search

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

HIDE SMILES / InChI

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	C22H25N7O5
Molecular Weight	467.4778
Charge	0
Count

Stereochemistry	EPIMERIC
Additional Stereochemistry	No
Defined Stereocenters	1 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9167747 | https://www.ncbi.nlm.nih.gov/pubmed/9279889

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
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/6690069	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Renal cell carcinoma 31 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9167747	Primary	Withdrawn	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9443617	Primary	Phase II 1132	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9279889	Palliative	Preclinical	Unknown Approved Use Unknown

C_max

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	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	LEUCOVORIN	EDATREXATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

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	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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 Page: p.277	DLT: Stomatitis, Diarrhea... Dose limiting toxicities: Stomatitis (grade 4, 66.7%) Diarrhea (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 Page: p.277	Sources: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/12094542 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: https://pubmed.ncbi.nlm.nih.gov/12094542 Page: p.476	Sources: https://pubmed.ncbi.nlm.nih.gov/12094542 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: https://pubmed.ncbi.nlm.nih.gov/9816135 Page: p.1822	unhealthy n = 3 Health Status: unhealthy Condition: cancer Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/9816135 Page: p.1822	Disc. AE: Leukoencephalopathy... AEs leading to discontinuation/dose reduction: Leukoencephalopathy (33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/9816135 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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/10037175 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: https://pubmed.ncbi.nlm.nih.gov/9816135 Page: p.1822	unhealthy n = 3 Health Status: unhealthy Condition: cancer Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/9816135 Page: p.1822

Sourcing

Vendor/Aggregator	ID	URL
ABI Chem	AC1OCESK
Achemtek	0102-012604	http://www.achemtek.com/80576-83-6
ChemMol	99170334	http://www.chemmol.com/chemmol/99170334.html
Chemieliva Pharmaceutical Co., Ltd	PBCM0847659
MuseChem	I006589	https://www.musechem.com/product/I006589.html
NovoSeek	6917908
OChem	21433	http://www.ocheminc.com/index.php?act=psearch&pid=576E836
Smolecule	S548911	http://www.smolecule.com/products/s548911
THE BioTek	bt-288315	https://www.thebiotek.com/product/inhibitors/bt-288315
Yick-Vic Chemicals & Pharmaceuticals (HK) Ltd.	PH-5862
eNovation Chemicals	D672812	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672812
iChemical	EBD1374	http://www.ichemical.com/chemicals/cas-80576-83-6

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	1501226
Schedule-dependent synergism of edatrexate and cisplatin in combination in the A549 lung-cancer cell line as assessed by median-effect analysis.	1993	8269606
Schedule-dependent synergism of taxol or taxotere with edatrexate against human breast cancer cells in vitro.	1996	8529281
Phase II trial of edatrexate plus carboplatin in metastatic non-small-cell lung cancer: a Southwest Oncology Group study.	1997	9443617
Phase I trial of edatrexate plus carboplatin in advanced solid tumors: amelioration of dose-limiting mucositis by ice chip cryotherapy.	1998	9740546
The role of circulating immune complexes and biocompatibility of staphylococcal protein A immunoadsorption in mitomycin C-induced hemolytic uremic syndrome.	2004 Oct	15384034

Patents

Sample Use Guides

In Vivo Use Guide

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 19:57:47 GMT 2023` Edited by `admin` on `Sat Dec 16 19:57:47 GMT 2023`
Record UNII	5KMD2L467S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

EDATREXATE MONOHYDRATE

Common Name

English

L-Glutamic acid, N-[4-[1-[(2,4-diamino-1,7-dihydro-7-oxo-6-pteridinyl)methyl]propyl]benzoyl]-, monohydroate

Systematic Name

English

Code System Code Type Description

FDA UNII

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

PRIMARY

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EDATREXATE

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/9167747 | https://www.ncbi.nlm.nih.gov/pubmed/9279889

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9167747 | https://www.ncbi.nlm.nih.gov/pubmed/9279889

C_max

T_1/2