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
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)
| 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 |
DescriptionSources: http://www.ema.europa.eu/docs/en_GB/document_library/Orphan_designation/2009/10/WC500006236.pdfCurator's Comment: Description was created based on several sources, including http://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=42223
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
Cmax
| 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 | Co-administered | 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 |
T1/2
| Value | Dose | Co-administered | 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 |
Funbound
| 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Characterization and drug sensitivity of four newly established colon adenocarcinoma cell lines to antifolate inhibitors of thymidylate synthase. | 2001 |
|
| A phase I study of nolatrexed dihydrochloride in children with advanced cancer. A United Kingdom Children's Cancer Study Group Investigation. | 2001 Jan 5 |
|
| Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer. | 2001 Nov |
|
| 2-[11C]thymidine positron emission tomography as an indicator of thymidylate synthase inhibition in patients treated with AG337. | 2003 May 7 |
|
| [Effects of nolatrexed on thymidylate synthase protein expression]. | 2004 Aug |
|
| Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma. | 2004 Jan 12 |
|
| Nucleobase- and p-glycoprotein-mediated transport of AG337 in a Caco-2 cell culture model. | 2004 May-Jun |
|
| Low folate conditions may enhance the interaction of trifluorothymidine with antifolates in colon cancer cells. | 2006 Jan |
|
| Elevation of radiolabelled thymidine uptake in RIF-1 fibrosarcoma and HT29 colon adenocarcinoma cells after treatment with thymidylate synthase inhibitors. | 2006 Sep |
|
| Phase II trial of nolatrexed dihydrochloride [Thymitaq, AG 337] in patients with advanced hepatocellular carcinoma. | 2007 Feb |
|
| Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part II. | 2008 Feb |
|
| [Preparation of long-circulating nolatrexed dihydrochloride liposomes and its antitumor activity]. | 2008 Mar |
|
| Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study. | 2010 Feb |
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 17:35:33 UTC 2023
by
admin
on
Sat Dec 16 17:35:33 UTC 2023
|
| Record UNII |
K75ZUN743Q
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
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 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
||
|
FDA ORPHAN DRUG |
148801
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
||
|
NCI_THESAURUS |
C2021
Created by
admin on Sat Dec 16 17:35:34 UTC 2023 , Edited by admin on Sat Dec 16 17:35:34 UTC 2023
|
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
CHEMBL320775
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
135400184
Created by
admin on Sat Dec 16 17:35:34 UTC 2023 , Edited by admin on Sat Dec 16 17:35:34 UTC 2023
|
PRIMARY | |||
|
C099178
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
100000083585
Created by
admin on Sat Dec 16 17:35:34 UTC 2023 , Edited by admin on Sat Dec 16 17:35:34 UTC 2023
|
PRIMARY | |||
|
NOLATREXED
Created by
admin on Sat Dec 16 17:35:34 UTC 2023 , Edited by admin on Sat Dec 16 17:35:34 UTC 2023
|
PRIMARY | |||
|
C143088
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
SUB09342MIG
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
7683
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
K75ZUN743Q
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
147149-76-6
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
m8029
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | Merck Index | ||
|
DB12912
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY | |||
|
DTXSID3048281
Created by
admin on Sat Dec 16 17:35:33 UTC 2023 , Edited by admin on Sat Dec 16 17:35:33 UTC 2023
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
SALT/SOLVATE -> PARENT |
|
||
|
|
TARGET -> INHIBITOR |
|
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |
|
