AG2034: A novel inhibitor of glycinamide ribonucleotide formyltransferase

Investigational New Drugs

Volumn 14, Issue 3, 1996, Pages 295-303

  Boritzki, Theodore J ^a   Barlett, Charlotte A ^a   Zhang, Cathy ^a   Howland, Eleanor F ^a   Margosiak, Stephen A ^a   Palmer, Cindy L ^a   Romines, William H ^a   Jackson, Robert C ^a  

^a AGOURON PHARMACEUTICALS INC   (United States)

Author keywords

AG2034; Antifolate; Glycinamide ribonucleotide formyltransferase

Indexed keywords

5 AMINO 4 IMIDAZOLECARBOXAMIDE; ENZYME INHIBITOR; FOLIC ACID; FOLYLPOLYGLUTAMATE SYNTHASE; HYPOXANTHINE; N [[5 [2 (2 AMINO 4,6,7,8 TETRAHYDRO 4 OXO 1H PYRIMIDO[5,4 B][1,4]THIAZIN 6 YL)ETHYL] 2 THIENYL]CARBONYL]GLUTAMIC ACID; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; RECEPTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL TRANSPORT; CULTURE MEDIUM; GROWTH INHIBITION; HUMAN; HUMAN CELL; LIVER; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECEPTOR AFFINITY; X RAY ANALYSIS; XENOGRAFT;

ACYLTRANSFERASES; ANIMALS; ANTINEOPLASTIC AGENTS; DRUG SCREENING ASSAYS, ANTITUMOR; ENZYME INHIBITORS; FEMALE; FOLIC ACID ANTAGONISTS; GLUTAMATES; HUMANS; HYDROXYMETHYL AND FORMYL TRANSFERASES; MICE; MICE, INBRED C3H; NEOPLASMS, EXPERIMENTAL; PHOSPHORIBOSYLGLYCINAMIDE FORMYLTRANSFERASE; PYRIMIDINES; RATS; TRANSPLANTATION, HETEROLOGOUS; TUMOR CELLS, CULTURED;

EID: 0029846266     PISSN: 01676997     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF00194533     Document Type: Article

References (25)

1. Fry DW, Besserer JA, Boritzki TJ: Transport of the antitumor antibiotic CI-920 into L1210 leukemia cells by the reduced folate carrier. Cancer Res 44:3366-3370, 1984
2. Beardsley GP, Taylor EC, Grindey GB, Moran RG: Deaza derivatives of tetrahydrofolic acid. In: Cooper BA, Whitehead VM (eds) A New Class of Folate Antimetabolite, Chemistry and Biology of Pteridines. De Gruyter, Berlin, 1986, pp 953-957
3. Shih C, Grindey GB, Houghton PJ, Houghton JA: In vivo antitumor activity of 5-,10 dideazatetrahydrofolic acid (DDATHF) and its diastereomeric isomers. Proc Am Assoc Cancer Res 29:1125, 1988
4. Grindey GB, Alati T, Shih C: Reversal of the toxicity but not the antitumor activity of lometrexol by folic acid. Proc Am Assoc Cancer Res 32:324, 1991
5. Alati T, Shih C, Pohland RC, Lantz RJ, Grindey GB: Evaluation of the mechanism(s) of inhibition of the toxicity, but not the antitumor activity of lometrexol. Proc Am Assoc Cancer Res 33:2432, 1992
6. Young C, Currie V, Baltzer L, Trochanowski B, Eton O, Dyke R, Bowsher R: Phase I and clinical pharmacologic study of LY264618, 5,10-dideazatetrahydrofolate. Proc Am Assoc Cancer Res 31:1053, 1990
7. Ray MS, Muggia FM, Leichmann CG, Grunberg SM, Nelson RL, Dyke RW, Moran RG: Phase I study of (6R)-5,10-dideazatetrahydrofolate: a folate antimetabolite inhibitory to de novo purine synthesis. J NCI 85:1154-1159, 1993
8. Wedge SR, Laohavinij S, Taylor GA, Newell DR, Proctor M, Chapman F, Simmons D, Oakey A, Gumbrell L, Calvert AH: A phase I study of the antipurine antifolate lometrexol administered with an oral folic acid supplement. Proc BRS, 1994, 498 p
9. Wedge SR, Laohavinij S, Taylor GA, Newell DR, Charlton CJ, Proctor M, Chapman F, Simmons D, Oakey A, Gumbrell L, Calvert AH: Modulation of lometrexol toxicity by oral folic acid administration: a phase I study. Proc Am Assoc Cancer Res 34:1629, 1993
10. Cole JT, Gralla RJ, Kardinal CG, Rivera NP: Lometrexol (DDATHF): phase I trial of a weekly schedule of this new antifolate. Proc Am Assoc Cancer Res 33:2468, 1992
11. Jackson RC, Harkrader RJ: The contributions of de novo and salvage pathways of nucleotide biosynthesis in normal and malignant cells. In: Tattersall MHN, Fox RM (eds) Nucleosides and Cancer Treatment. Academic Press, Sydney, 1981, pp 18-31
12. Smith SG, Lehman NL, Moran RG: Cytotoxicity of antifolate inhibitors of thymidylate and purine synthesis to WiDR colonic carcinoma cells. Cancer Res 53:5697-5706, 1993
13. Smith GK, Duch DS, Dev IK, Kaufmann SH: Metabolic effects and kill of human T-cell leukemia by 5-deazaacyclotetrahydrofolate, a specific inhibitor of glycinamide ribonucleotide transformylase. Cancer Res 52:4895-4903, 1992
14. Almassy RJ, Janson CA, Kan CC, Hostomska Z: Structure of Apo and complexed Escherichia coli glycinamide ribonucleotide transformylase. Proc Natl Acad Sci USA 89:6114-6118, 1992
15. Goodford PJ: A computational procedure for determining energetically favorable binding sites on biologically important macromolecules. J Med Chem 28:849-857, 1985
16. Young M, Sammons D, Mueller WT, Benkovic SJ: An antibody probe to determine the native species of glycinamide ribonucleotide transformylase in chicken liver. Biochemistry 23:3979-3986, 1984
17. Kan CC, Gehring MR, Nodes BR, Janson CA, Almassy RJ, Hostomska Z: Heterologous expression and purification of active human phosphoribosylglycinamide formyltransferase as a single domain. J Prot Chem 11:467-473, 1992
18. Morrison JF: Kinetics of the reversible inhibition of enzyme-catalyzed reactions by tight-binding inhibitors. Biochem Biophys Acta 185:269-286, 1969
19. Saikawa Y, Knight CB, Saikawa T, Page ST, Chabner BA, Elwood PC: Decreased expression of the human folate receptor mediates transport-defective methotrexate resistance in KB cells. J Biol Chem 268:5293-5301, 1993
20. Elwood PC, Kane MA, Portillo RM, Kolhouse JF: The isolation, characterization, and comparison of the membrane-associated and soluble folate-binding proteins from KB cells. J Biol Chem 261:15416-15423, 1986
21. Moran RG, Colman PD: Mammalian folyl polyglutamate synthetase: partial purification and properties of the mouse liver enzyme. Biochemistry 23:4580-4589, 1984
22. Moran RG, Colman PD: Measurement of folylpolyglutamate synthetase in mammalian tissues. Anal Biochem 140:326-342, 1984
23. Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assay. J Immunol Meth 65:55-63, 1983
24. Jackson RC: The Theoretical Foundations of Cancer Chemotherapy Introduced by Computer Models. Academic Press, San Diego, 1992
25. Matlashewski G, Banks L, Pim D, Crawford L: Analysis of human p53 proteins and mRNA levels in normal and transformed cells. Eur J Biochem 154:665-672, 1986