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Nolatrexed(AG-337)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Nolatrexed(AG-337)图片
CAS NO:152946-68-4
规格:98%
分子量:357.26
包装与价格:
包装价格(元)
10mg电议
50mg电议

产品介绍
Non-classical thymidylate synthase inhibitor
CAS:152946-68-4
分子式:C14H14Cl2N4OS
分子量:357.26
纯度:98%
存储:Store at -20°C

Background:

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.
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