NOLATREXED DIHYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H12N4OS.2ClH
Molecular Weight	357.258
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.Cl.CC1=C(SC2=CC=NC=C2)C3=C(C=C1)N=C(N)NC3=O

InChI

InChIKey=PJKVJJYMWOCLIJ-UHFFFAOYSA-N

InChI=1S/C14H12N4OS.2ClH/c1-8-2-3-10-11(13(19)18-14(15)17-10)12(8)20-9-4-6-16-7-5-9;;/h2-7H,1H3,(H3,15,17,18,19);2*1H

HIDE SMILES / InChI

Molecular Formula	C14H12N4OS
Molecular Weight	284.336
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2009/10/WC500006236.pdf
Curator's Comment: Description was created based on several sources, including http://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=42223

The dihydrochloride salt of nolatrexed, a water-soluble lipophilic quinazoline folate analog with antineoplastic activity. Nolatrexed occupies the folate binding site of thymidylate synthase, resulting in inhibition of thymidylate synthase activity and thymine nucleotide synthesis with subsequent inhibition of DNA replication, DNA damage, S-phase cell cycle arrest, and caspase-dependent apoptosis. This agent also exhibits radiosensitizing activity. Orphan designation of nolatrexed was granted in the Unites States of America for treatment of hepatocellular carcinoma.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Thymidylate synthase 32 Target ID: CHEMBL1952 Sources: http://www.apexbt.com/nolatrexed-ag-337.html	Inhibitor 8297		11.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatocellular carcinoma 83 Sources: http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2009/10/WC500006236.pdf	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
24 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9508200	1040 mg/m² 1 times / day multiple, intravenous dose: 1040 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:		NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9918208	250 mg/m² 4 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
107 mg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9508200	904 mg/m² 1 times / day multiple, intravenous dose: 904 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
131 mg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9508200	1040 mg/m² 1 times / day multiple, intravenous dose: 1040 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3.1 μg × min/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9918208	250 mg/m² 4 times / day multiple, oral dose: 250 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
298 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9508200	904 mg/m² 1 times / day multiple, intravenous dose: 904 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
203 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9508200	1040 mg/m² 1 times / day multiple, intravenous dose: 1040 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
97 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815922	1350 mg/m² single, intravenous dose: 1350 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2.75% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815922	1350 mg/m² single, intravenous dose: 1350 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		NOLATREXED plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P01CC92	https://www.1pchem.com/search?query=1P01CC92
AK Scientific	8186AH	https://aksci.com/item_detail.php?cat=8186AH
AK Scientific	O382	https://aksci.com/item_detail.php?cat=O382
Angene	AGN-PC-0JLG5J	http://www.angenechemical.com/productshow/AGN-PC-0JLG5J.html
ApexBio Technology	B5892	https://www.apexbt.com/catalogsearch/result/?q=B5892
Axon MedChem	2853	https://www.axonmedchem.com/product/2853
BOC Sciences	147149-76-6	http://www.bocsci.com/description.asp?cas=147149-76-6
BOC Sciences	152946-68-4	http://www.bocsci.com/description.asp?cas=152946-68-4
Chem Scene	CS-0028903	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0028903
Excenen	EX-A2112	http://www.excenen.com/searchresultlist.php?id=EX-A2112
Lab Network	LN01306589	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01306589
Lab Network	LN01806156	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01806156
Lab Seeker	SC-18884	http://www.labseeker.com/search.php?keywords=SC-18884&category=0
LabSeeker	SC-18884	http://www.labseeker.com/search.php?keywords=SC-18884&category=0
MedChem Express	HY-108474	https://www.medchemexpress.com/search.html?q=HY-108474&ft=&fa=&fp=
MolPort	MolPort-005-935-365	https://www.molport.com/shop/molecule-link/MolPort-005-935-365
MolPort	MolPort-016-638-439	https://www.molport.com/shop/molecule-link/MolPort-016-638-439
MolPort	MolPort-035-394-976	https://www.molport.com/shop/molecule-link/MolPort-035-394-976
MuseChem	R008557	https://www.musechem.com/product/R008557.html
MuseChem	R011020	https://www.musechem.com/product/R011020.html
PI Chemicals	PI-36644	http://www.pipharm.com/catalog_products/PI-36644.html
Ryan Scientific	RI-2	https://ryansci.com/products?q=RI-2&list_q=&search_type=exact
ShangHai Biochempartner	BCP02372	http://www.biochempartner.com/search_BCP02372
ShangHai Biochempartner	BCP12638	http://www.biochempartner.com/search_BCP12638
Tetrahedron	TS54748	http://www.thsci.com/search.do?q=TS54748
Tetrahedron	TS79378	http://www.thsci.com/search.do?q=TS79378
Toronto Research Chemicals	N635800	https://www.trc-canada.com/product-detail/?CatNum=N635800
eMolecules	2728791	https://orderbb.emolecules.com/search/#?query=2728791
eMolecules	300853761	https://orderbb.emolecules.com/search/#?query=300853761
eMolecules	45916648	https://orderbb.emolecules.com/search/#?query=45916648
eMolecules	64094759	https://orderbb.emolecules.com/search/#?query=64094759
eMolecules	8796923	https://orderbb.emolecules.com/search/#?query=8796923
eNovation Chemicals	D501905	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501905&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3223857505	https://mcule.com/MCULE-3223857505/
mcule	MCULE-8115720426	https://mcule.com/MCULE-8115720426/

PubMed

Title	Date	PubMed
[Effects of nolatrexed on thymidylate synthase protein expression].	2004 Aug	15321751
Phase III randomized controlled trial comparing the survival of patients with unresectable hepatocellular carcinoma treated with nolatrexed or doxorubicin.	2007 Jul 20	17634485
[Preparation of long-circulating nolatrexed dihydrochloride liposomes and its antitumor activity].	2008 Mar	18359701

Sample Use Guides

In Vivo Use Guide

Nolatrexed can be safely administered as an oral preparation at a dose of 800 mg/m2/day for 5 days.

Route of Administration: Oral

In Vitro Use Guide

In HT29 cells, exposure to nolatrexed (5 uM) for 24 h induced S-phase cell cycle arrest. In HCT116 cells, exposure to nolatrexed (5 lM) for 24 h also induced S-phase arrest with the cell population significantly increasing during this phase from 24% to 40%.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:53:59 GMT 2023` Edited by `admin` on `Fri Dec 15 17:53:59 GMT 2023`
Record UNII	1XA69O733O
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NOLATREXED DIHYDROCHLORIDE

Common Name

English

NOLATREXED DIHYDROCHLORIDE [MI]

Common Name

English

2-AMINO-3,4-DIHYDRO-6-METHYL-4-OXO-5-(4-PYRIDYLTHIO)-QUINAZOLINE DIHYDROCHLORIDE

Systematic Name

English

AG-337

Code

English

4(1H)-QUINAZOLINONE, 2-AMINO-6-METHYL-5-(4-PYRIDINYLTHIO)-, HYDROCHLORIDE (1:2)

Systematic Name

English

AG 337

Code

English

4(1H)-QUINAZOLINONE, 2-AMINO-6-METHYL-5-(4-PYRIDINYLTHIO)-, DIHYDROCHLORIDE

Common Name

English

THYMITAQ

Brand Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2021