The purine path to chemotherapy
Abstract
Research on antimetabolites of nucleic acid purines led to drugs for the treatment of acute leukemia (6-mercaptopurine and thioguanine), gout and hyperuricemia (allopurinol), and herpesvirus infections (acyclovir), and for the prevention of organ transplant rejection (azathioprine).
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6-MP and 6-TG inhibit PRPP amidotransferase, the first enzyme in de novo purine biosynthesis, and have been successful in treating many cancers including childhood leukemia.
“Notable examples include the purine analogues 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG), which inhibit 5-phosphoribosyl-1-pyrophosphatase (PRPP) amidotransferase, the first enzyme in de novo purine biosynthesis (Figure 1a, Figure 2b). 6-MP and 6-TG have been successful in treating many cancers including childhood leukemia (Elion, 1989).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Elion, 1989
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Self-citationSpector, T., Jones, T., & Beacham, L. M. (1983) · Biochemical Pharmacology · doi:10.1016/0006-2952(83)90010-2 · Cited by 37 · see citing works
Effects of Purine Derivatives and Analogues on Multiplication of the Vaccinia Virus
Thompson, R. L., Price, M. L., Minton, S. A., et al. (1950) · The Journal of Immunology · doi:10.4049/jimmunol.65.5.529 · Cited by 36 · see citing works
Massey, V., Komai, H., Palmer, G., et al. (1971) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60909-7 · Cited by 36 · see citing works
Metabolic and therapeutic effects of allopurinol in patients with leukemia and gout
Vogler, W. R., Bain, J. A., Huguley, C. M., et al. (1966) · The American Journal of Medicine · doi:10.1016/0002-9343(66)90118-5 · Cited by 36 · see citing works
ANTAGONISTS OF NUCLEIC ACID DERIVATIVES
Elion, G. B., & Hitchings, G. H. (1950) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)56352-3 · Cited by 35 · see citing works
Self-citationRw, R., László, J., Itoga, T., et al. (1961) · PubMed · Cited by 35 · see citing works
Larkin, M., OGILVIE, M. M., & McGill, J. I. (1983) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/12.1.79 · Cited by 34 · see citing works
Experimental, clinical, and metabolic studies of thiopurines.
Eb, E., Sw, C., Hitchings, G. H., et al. (1962) · PubMed · Cited by 32 · see citing works
THE LIMITATIONS OF INHIBITION ANALYSIS
Hitchings, G. H., Elion, G. B., & Vanderwerff, H. (1948) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)57311-7 · Cited by 31 · see citing works
Self-citationMetabolic disposition of acyclovir in the guinea pig, rabbit, and monkey
Good, S. S., & de Miranda, P. (1982) · The American Journal of Medicine · doi:10.1016/0002-9343(82)90071-7 · Cited by 29 · see citing works
Selectivity--key to chemotherapy: presidential address.
Elion, G. B. (1985) · PubMed · Cited by 27 · see citing works
Self-citationThe effects of 6-mercaptopurine on Lactobacillus casei
Balis, M. E., Levin, D. H., Brown, G. B., et al. (1957) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(57)90046-2 · Cited by 26 · see citing works
Chen, H. Y., & Williams, J. D. (1983) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/12.1.19 · Cited by 24 · see citing works
Antipurines and Purine Metabolism
Wolberg, G. (1988) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-73217-1_24 · Cited by 21 · see citing works
Allopurinol in the Prophylaxis of Uric Acid Stones
de Vries, A., Frank, M., Liberman, U. A., et al. (1966) · Annals of the Rheumatic Diseases · doi:10.1136/ard.25.suppl_6.691 · Cited by 21 · see citing works
Suppression of the Immune Response by Drugs in Combination
Bieber, S., Elion, G. B., Hitchings, G. H., et al. (1962) · Experimental Biology and Medicine · doi:10.3181/00379727-111-27783 · Cited by 21 · see citing works
Self-citationde Flines, J. (1955) · Journal of the American Chemical Society · doi:10.1021/ja01611a083 · Cited by 21 · see citing works
The metabolism of 2-amino-6-[(1-methyl-4-nitro-5-imidazolyl)thio]purine (B.W. 57-323) in man.
Elion, G. B., Sw, C., Hitchings, G. H., et al. (1960) · PubMed · Cited by 20 · see citing works
Self-citation45. The action of phosphorus pentasulphide on barbituric acids
Carrington, H. C. (1944) · Journal of the Chemical Society (Resumed) · doi:10.1039/jr9440000124 · Cited by 18 · see citing works
Layer on layer: the Bruce F. Cain memorial Award lecture.
Hitchings, G. H., & Elion, G. B. (1985) · PubMed · Cited by 18 · see citing works
Self-citationElion, G. B., Bieber, S., & Hitchings, G. H. (1960) · PubMed · Cited by 18 · see citing works
Self-citationThe metabolic disposition of 14C-azathioprine in the dog.
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Xanthine oxidase inhibition in the management of hyperuricemia in leukemias and lymphomas
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Hormone-treated primary operable breast carcinoma.A pathological study of thirty-three cases
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KIDNEY TRANSPLANTATION TRENDS FROM UCLA REGISTRY DATA, 1975-1982
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Savage, O. A. (1966) · Annals of the Rheumatic Diseases · doi:10.1136/ard.25.suppl_6.599 · Cited by 5 · see citing works
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- Authors
- Elion, G. B.
- Affiliations
- Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, NC 27709.
- Corresponding author
- Elion, Gertrude B.
- Venue
- Science
- Published
- 1989-04-07
- Volume
- 244
- Issue
- 4900
- Pages
- 41-47
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2028547310
- Cited by
- 687
- References
- 135
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 17 · 2023: 16 · 2022: 28 · 2021: 23 · 2020: 22 · 2019: 22 · 2018: 23 · 2017: 31 · 2016: 27 · 2015: 24 · 2014: 27 · 2013: 23 · 2012: 26
- FWCI
- 0.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Historical Medical Research and Treatments
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and Characterization of Heterocyclic Compounds
- Keywords
- purine analogues, nucleic acid metabolism, 6-mercaptopurine, 6-thioguanine, allopurinol, acyclovir, azathioprine, acute leukemia, gout, hyperuricemia, herpesvirus infection, organ transplant rejection, chemotherapy
- MeSH terms
- Animals, Drug Therapy, Humans, Purines
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