Nolatrexed (AG-337) (Synonyms: AG337) |
Catalog No.GC14681 |
Nolatrexed (AG-337) (AG 337) est un inhibiteur lipophile non compétitif de la thymidylate synthase, interagit au niveau du site de liaison du cofacteur folate de l'enzyme, avec un Ki de 11 nM pour la thymidylate synthase humaine. Nolatrexed (AG-337) (AG 337) induit l'arrêt du cycle cellulaire en phase S des cellules cancéreuses. Activité anticancéreuse.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 152946-68-4
Sample solution is provided at 25 µL, 10mM.
Description:
IC50: 1.0, 0.81 and 1.0 μM for L1210, CCRF-CEM and GC3/M TK- cell lines, respectively
Thymidylate synthase (TS) is a crucial enzyme in the synthesis of 2'-deoxythymidine-5'-monophosphate, an essential precursor for DNA biosynthesis. Thus, this enzyme is a critical target in cancer chemotherapy. Nolatrexed (AG-337) is a non-classical thymidylate synthase inhibitor.
In vitro: Nolatrexed was designed using X-ray crystallographic data from the TS molecular modeling and folate binding site. It is a non-classical TS inhibitor in that it lacks a terminal glutamate side chain and is uncharged at physiological pH. Nolatrexed does not require a specific transport mechanism to enter into cells and, once within the cell, is not a substrate for the enzyme folyl polyglutamate synthetase [1].
In vivo: When nolatrexed was administered to nude mice bearing Bu25TK- tumor xenografts, a time-dependent increase in antitumor activity was observed [1].
Clinical trial: Phase I clinical studies showed that Nolatrexed can be safely administered to cancer patients at a dose of 800 mg/m2/d over 5 days by continuous intravenous infusion and this schedule is associated with antitumor effects [2].
Reference:
[1] Hughes AN, Rafi I, Griffin MJ, Calvert AH, Newell DR, Calvete JA, Johnston A, Clendeninn N, Boddy AV. Phase I studies with the nonclassical antifolate nolatrexed dihydrochloride (AG337, THYMITAQ) administered orally for 5 days. Clin Cancer Res. 1999 Jan;5(1):111-8.
[2] Rafi I, Boddy AV, Calvete JA, Taylor GA, Newell DR, Bailey NP, Lind MJ, Green M, Hines J, Johnstone A, Clendeninn N, Calvert AH. Preclinical and phase I clinical studies with the nonclassical antifolate thymidylate synthase inhibitor nolatrexed dihydrochloride given by prolonged administration in patients with solid tumors. J Clin Oncol. 1998 Mar;16(3):1131-41.
Average Rating: 5
(Based on Reviews and 8 reference(s) in Google Scholar.)GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.
Required fields are marked with *