Effects of Allopurinol and Oxipurinol on Pyrimidine Biosynthesis in Man

1974 ◽  
pp. 609-619 ◽  
Author(s):  
T. D. Beardmore ◽  
W. N. Kelley
Keyword(s):  
Pyrimidine Biosynthesis

scholarly journals 3-Methylaspartic Acid as a Potent Antimetabolite of Aspartic Acid in Pyrimidine Biosynthesis

1960 ◽  
Vol 235 (11) ◽  
pp. 3238-3241
Author(s):  
D.W. Woolley ◽  
Conrad Maugé ◽  
Monica Cassidy
Keyword(s):  
Aspartic Acid ◽  
Pyrimidine Biosynthesis ◽  
Methylaspartic Acid

scholarly journals Control of Pyrimidine Biosynthesis in Human Lymphocytes

1973 ◽  
Vol 248 (13) ◽  
pp. 4782-4785
Author(s):  
Kazuhiko Ito ◽  
Haruto Uchino
Keyword(s):  
Human Lymphocytes ◽  
Pyrimidine Biosynthesis

scholarly journals Pathway of Pyrimidine Biosynthesis in Premetamorphic Tadpoles

1964 ◽  
Vol 239 (7) ◽  
pp. 2239-2245
Author(s):  
Raymond H. Lindsay ◽  
Hachiro Nakagawa ◽  
Philip P. Cohen
Keyword(s):  
Pyrimidine Biosynthesis

scholarly journals Effects of acivicin and dichloroallyl lawsone upon pyrimidine biosynthesis in mouse L1210 leukemia cells.

1986 ◽  
Vol 261 (32) ◽  
pp. 14891-14895
Author(s):  
A J Kemp ◽  
S D Lyons ◽  
R I Christopherson
Keyword(s):  
Pyrimidine Biosynthesis ◽  
Leukemia Cells ◽  
L1210 Leukemia

scholarly journals Helicobacter pylori-selective Antibacterials Based on Inhibition of Pyrimidine Biosynthesis

2000 ◽  
Vol 275 (43) ◽  
pp. 33373-33378 ◽  
Author(s):  
Robert A. Copeland ◽  
Jovita Marcinkeviciene ◽  
Tasir S. Haque ◽  
Lisa M. Kopcho ◽  
Wenjun Jiang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Pyrimidine Biosynthesis

CSIG-11. KINASE-DIRECTED INHIBITION OF PYRIMIDINE BIOSYNTHESIS IN PTEN-DEFICIENT GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi35-vi35
Author(s):  
Pranjal Sarma ◽  
Kelli N Ennis ◽  
Catherine A Behrmann ◽  
Collin Wetzel ◽  
Biplab Dasgupta ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Tyrosine Kinases ◽  
Pyrimidine Biosynthesis ◽  
Flux Analysis ◽  
Glioblastoma Cells ◽  
Nucleotide Biosynthesis ◽  
Pten Loss ◽  
Frontline Treatment ◽  
Survival Signaling ◽  
Cytotoxic Responses

Abstract Targeting pyrimidine biosynthesis has been a mainstay of chemotherapy in oncology, including frontline treatment of pancreatic, breast, and colorectal carcinomas. In glioblastoma, the targeting pyrimidine biosynthesis is a promising emerging approach for counteracting the effects of PTEN-deficiency in glioblastoma. PTEN loss triggers the activation of mTORC1, which in turn phosphorylates and activates the ribosomal protein kinases S6K1 and S6K2. We have previously shown that combination treatment of inhibitors targeting S6K1 and the TYRO3-AXL-MERTK receptor tyrosine kinases (TAM-RTKs) triggers cytotoxic responses in PTEN-deficient glioblastoma cells. Here we show brain-penetrant inactivation of S6K1 and TAM-RTKs using the S6K1 inhibitor LY-2584702 and the TAM-RTK inhibitor BMS-777607, which reduced glioblastoma tumor growth. Pharmacogenetic analysis of signal transduction indicated a key role for S6K2 in sustaining survival signaling in PTEN-deficient glioblastoma cells. Steady-state metabolomics revealed that combined inactivation of S6K1 and TAM-RTKs resulted in decreased nucleotide biosynthesis, and flux analysis indicated reduced flux of glucose to pyrimidines. Altogether the results indicate a kinase-directed therapeutic strategy for targeting S6K1 and TAM-RTKs to reduce pyrimidine biosynthesis and glioblastoma tumor growth.

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