| Identification | More | [Name]
Nolatrexed dihydrochloride | [CAS]
152946-68-4 | [Synonyms]
3,4-dihydro-2-amino-6-methyl-4-oxo-5-(4-pyridylthio)-quinazoline dihydrochloride
NOLATREXED DIHYDROCHLORIDE
NOLATREXED HCL
NOLATREXED 2HCL
AG 337
2-Amino-6-methyl-5-(4-pyridinylthio)-4(1H)-quinazolinone Hydrochloride
Thymitaq | [EINECS(EC#)]
680-267-3 | [Molecular Formula]
C14H14Cl2N4OS | [MDL Number]
MFCD00917041 | [Molecular Weight]
357.26 | [MOL File]
152946-68-4.mol |
| Chemical Properties | Back Directory | [Appearance]
Tan Solid | [Melting point ]
301-3020C | [storage temp. ]
Hygroscopic, -20°C Freezer, Under Inert Atmosphere | [solubility ]
Methanol, Water | [form ]
Solid | [pka]
4.1; 5.9; 9.8(at 25℃) | [color ]
Off-White to Pale Yellow | [Usage]
Antifolate thymidylate synthase inhibitor. Antineoplastic. | [Stability:]
Hygroscopic | [CAS DataBase Reference]
152946-68-4(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Chemical Properties]
Tan Solid | [Uses]
Antifolate thymidylate synthase inhibitor. Antineoplastic. | [Biological Activity]
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]. | [IC 50]
1.0, 0.81 and 1.0 μm for l1210, ccrf-cem and gc3/m tk- cell lines, respectively | [storage]
Store at -20°C | [References]
[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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