Detail of "1173-82-6"

Reference

Biochemical effects of a quinazoline inhibitor of thymidylate synthetase, N-(4-(N-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)be nzoyl)-L-glutamic acid (CB3717), on human lymphoblastoid cells

Biochemical effects of a quinazoline inhibitor of thymidylate synthetase, N-(4-(N-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)be nzoyl)-L-glutamic acid (CB3717), on human lymphoblastoid cells. Jackson, Robert C.; Jackman, Ann L.; Calvert, A. Hilary (Lab. Exp. Oncol., Indiana Univ., Indianapolis, IN 46223, USA). Biochem. Pharmacol., 32(24), 3783-90 (English) 1983. CODEN: BCPCA6. ISSN: 0006-2952. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) The biochem. effects of the antitumor agent CB3717 (I) [76849-19-9] were studied in WI-L2 cultured human lymphoblastoid cells. CB3717 was a potent inhibitor of human thymidylate synthetase [9031-61-2]; the inhibition was competitive with 5,10-methylenetetrahydrofolate (Ki = 4.9 ′ 10-9M). CB3717 also inhibited human dihydrofolate reductase [9002-03-3], competitively with dihydrofolate (Ki = 2.3 ′ 10-8M). The growth-inhibitory effect of CB3717 could be prevented completely by 10 mM thymidine [50-89-5]. Administration of thymidine could be delayed for up to 8 h after CB3717 treatment without cytotoxicity but, if thymidine was delayed for 24 h, severe toxicity resulted. Incubation for 16 h in the presence of a growth-inhibitory concn. of CB3717 did not result in the appearance of dihydrofolate [4033-27-6] in WI-L2 cells. These results indicate that, in the presence of CB3717, thymidylate synthetase, rather than dihydrofolate reductase, became rate-limiting for the cycle of dihydrofolate oxidn. and redn. Treatment of cells for 16 h at an IC50 (50% inhibitory concn.) of CB3717 caused a decrease of 88% in cellular dTTP [365-08-2] and a 2,300% increase in dUMP [964-26-1]. The level of dUDP [4208-67-7] also increased, and traces of dUTP [1173-82-6] appeared in treated cells. No large changes were seen in ribonucleotide pools. A kinetic anal. was made, by computer simulation, of predicted consequences of metabolic effects of compds. that inhibit both dihydrofolate reductase and thymidylate synthetase. It was concluded that, even if the Ki of the inhibitor for thymidylate synthetase were 3 orders of magnitude higher (weaker) than the Ki for dihydrofolate reductase, thymidylate synthetase could still become rate-limiting.

Drosophila deoxyuridine triphosphatase

Drosophila deoxyuridine triphosphatase. Purification and characterization.Several substances are used for example 1173-82-6 and 37289-34-2 which are their cas registry numbers. Giroir, L. Eric; Deutsch, Walter A. (Dep. Biochem., Louisiana State Univ., Baton Rouge, LA 70803, USA). J. Biol. Chem., 262(1), 130-4 (English) 1987. CODEN: JBCHA3. ISSN: 0021-9258. DOCUMENT TYPE: Journal CA Section: 7 (Enzymes) Section cross-reference(s): 12 Deoxyuridine triphosphatase (dUTPase), an enzyme that catalyzes hydrolysis of dUTP to deoxyuridylate and inorg. pyrophosphate, was purified ~6000-fold from Drosophila embryos. The enzyme has a native mol. wt. of 46,000 and a sedimentation coeff. of 3.5 S. The enzyme is most likely a metalloenzyme. It is specific for dUTP among the DNA nucleotides tested, with an apparent Km of 1 mM. The expression of dUTPase appears state-specific, with embryos representing the only step in the life cycle of Drosophila with clearly detectable levels of the enzyme. Although other possibilities exist, these results suggest an enhanced opportunity for the inclusion of uracil into Drosophila DNA subsequent to embryonic development. .