152946-68-4 Usage
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
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.
Check Digit Verification of cas no
The CAS Registry Mumber 152946-68-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,2,9,4 and 6 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 152946-68:
(8*1)+(7*5)+(6*2)+(5*9)+(4*4)+(3*6)+(2*6)+(1*8)=154
154 % 10 = 4
So 152946-68-4 is a valid CAS Registry Number.
InChI:InChI=1/C14H12N4OS.2ClH/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);2*1H
