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Details

Stereochemistry ACHIRAL
Molecular Formula C14H12N4OS
Molecular Weight 284.336
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NOLATREXED

SMILES

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

InChI

InChIKey=XHWRWCSCBDLOLM-UHFFFAOYSA-N
InChI=1S/C14H12N4OS/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)

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

Description
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

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 11.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Sourcing

Vendor/AggregatorIDURL
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

PubMed

TitleDatePubMed
Serine/threonine protein phosphatase inhibition enhances the effect of thymidylate synthase inhibition.
2004 Mar
Antifolate inhibitors of thymidylate synthase as anticancer drugs.
2010 Nov

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Can also be administered at a dose of 500 mg m(-2) day(-1) as a 120-h continuous intravenous infusion in combination with paclitaxel. http://www.ncbi.nlm.nih.gov/pubmed/10789718
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 Sat Dec 16 17:35:33 GMT 2023
Edited
by admin
on Sat Dec 16 17:35:33 GMT 2023
Record UNII
K75ZUN743Q
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NOLATREXED
INN   MART.   MI   WHO-DD  
INN  
Official Name English
NOLATREXED [MI]
Common Name English
2-AMINO-6-METHYL-5-(4-PYRIDYLTHIO)-4(3H)-QUINAZOLINONE
Systematic Name English
2-AMINO-6-METHYL-5-(4-PYRIDINYLTHIO)-4(1H)-QUINAZOLINONE
Systematic Name English
NOLATREXED [MART.]
Common Name English
4(1H)-QUINAZOLINONE, 2-AMINO-6-METHYL-5-(4-PYRIDINYLTHIO)-
Systematic Name English
Nolatrexed [WHO-DD]
Common Name English
2-AMINO-3,4-DIHYDRO-6-METHYL-4-OXO-5-(4-PYRIDYLTHIO)QUINAZOLINE
Systematic Name English
nolatrexed [INN]
Common Name English
2-AMINO-6-METHYL-5-(PYRIDIN-4-YLSULFANYL)-3H-QUINAZOLIN-4-ONE
Systematic Name English
Classification Tree Code System Code
EU-Orphan Drug EU/3/03/165
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
FDA ORPHAN DRUG 148801
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
NCI_THESAURUS C2021
Created by admin on Sat Dec 16 17:35:34 GMT 2023 , Edited by admin on Sat Dec 16 17:35:34 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL320775
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
PUBCHEM
135400184
Created by admin on Sat Dec 16 17:35:34 GMT 2023 , Edited by admin on Sat Dec 16 17:35:34 GMT 2023
PRIMARY
MESH
C099178
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
SMS_ID
100000083585
Created by admin on Sat Dec 16 17:35:34 GMT 2023 , Edited by admin on Sat Dec 16 17:35:34 GMT 2023
PRIMARY
WIKIPEDIA
NOLATREXED
Created by admin on Sat Dec 16 17:35:34 GMT 2023 , Edited by admin on Sat Dec 16 17:35:34 GMT 2023
PRIMARY
NCI_THESAURUS
C143088
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
EVMPD
SUB09342MIG
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
INN
7683
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
FDA UNII
K75ZUN743Q
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
CAS
147149-76-6
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
MERCK INDEX
m8029
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY Merck Index
DRUG BANK
DB12912
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
EPA CompTox
DTXSID3048281
Created by admin on Sat Dec 16 17:35:33 GMT 2023 , Edited by admin on Sat Dec 16 17:35:33 GMT 2023
PRIMARY
Related Record Type Details
Structure of NOLATREXED DIHYDROCHLORIDE
SALT/SOLVATE -> PARENT
THYMIDYLATE SYNTHASE
TARGET -> INHIBITOR
Related Record Type Details
Structure of NOLATREXED
ACTIVE MOIETY
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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