Name: Nolatrexed (AG-337)
Price: 244.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    Description:IC50: 1.0, 0.81 and 1.0 μM for L1210, CCRF-CEM and GC3/M TK- cell lines, respectivelyThymidylate 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].
    
    [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.
- Properties
  - Alternative Name
    
    2-imino-6-methyl-5-(pyridin-4-ylthio)-1,2-dihydroquinazolin-4-ol dihydrochloride
    
    CAS Number
    
    152946-68-4
    
    Molecular Formula
    
    C14H14Cl2N4OS
    
    Molecular Weight
    
    357.26
    
    Appearance
    
    A solid
    
    Purity
    
    98.00%
    
    Solubility
    
    ≥108.6 mg/mL in H2O; ≥17.2 mg/mL in DMSO; ≥5.5 mg/mL in EtOH with ultrasonic
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only

Nolatrexed (AG-337)

Nolatrexed (AG-337)

Background

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