Tiazofurin

A new antitumor agent

Peter J. O'Dwyer, D. Dale Shoemaker, Hiremagalur N. Jayaram, David G. Johns, David A. Cooney, Silvia Marsoni, Louis Malspeis, Jacqueline Plowman, J. Paul Davignon, Ruth D. Davis

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90% of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalInvestigational New Drugs
Volume2
Issue number1
DOIs
StatePublished - Mar 1984
Externally publishedYes

Fingerprint

tiazofurin
Antineoplastic Agents
Pharmaceutical Preparations
Leukemia P388
Lewis Lung Carcinoma
Leukemia L1210
Inosine Monophosphate
Hyperuricemia
Allopurinol
Half-Life
Appointments and Schedules
Oxidoreductases
Urine

Keywords

  • tiazofurin

ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine

Cite this

O'Dwyer, P. J., Shoemaker, D. D., Jayaram, H. N., Johns, D. G., Cooney, D. A., Marsoni, S., ... Davis, R. D. (1984). Tiazofurin: A new antitumor agent. Investigational New Drugs, 2(1), 79-84. https://doi.org/10.1007/BF00173791

Tiazofurin : A new antitumor agent. / O'Dwyer, Peter J.; Shoemaker, D. Dale; Jayaram, Hiremagalur N.; Johns, David G.; Cooney, David A.; Marsoni, Silvia; Malspeis, Louis; Plowman, Jacqueline; Davignon, J. Paul; Davis, Ruth D.

In: Investigational New Drugs, Vol. 2, No. 1, 03.1984, p. 79-84.

Research output: Contribution to journalArticle

O'Dwyer, PJ, Shoemaker, DD, Jayaram, HN, Johns, DG, Cooney, DA, Marsoni, S, Malspeis, L, Plowman, J, Davignon, JP & Davis, RD 1984, 'Tiazofurin: A new antitumor agent', Investigational New Drugs, vol. 2, no. 1, pp. 79-84. https://doi.org/10.1007/BF00173791
O'Dwyer PJ, Shoemaker DD, Jayaram HN, Johns DG, Cooney DA, Marsoni S et al. Tiazofurin: A new antitumor agent. Investigational New Drugs. 1984 Mar;2(1):79-84. https://doi.org/10.1007/BF00173791
O'Dwyer, Peter J. ; Shoemaker, D. Dale ; Jayaram, Hiremagalur N. ; Johns, David G. ; Cooney, David A. ; Marsoni, Silvia ; Malspeis, Louis ; Plowman, Jacqueline ; Davignon, J. Paul ; Davis, Ruth D. / Tiazofurin : A new antitumor agent. In: Investigational New Drugs. 1984 ; Vol. 2, No. 1. pp. 79-84.
@article{52d254e2b9e94b7693b688f911273365,
title = "Tiazofurin: A new antitumor agent",
abstract = "Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90{\%} of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.",
keywords = "tiazofurin",
author = "O'Dwyer, {Peter J.} and Shoemaker, {D. Dale} and Jayaram, {Hiremagalur N.} and Johns, {David G.} and Cooney, {David A.} and Silvia Marsoni and Louis Malspeis and Jacqueline Plowman and Davignon, {J. Paul} and Davis, {Ruth D.}",
year = "1984",
month = "3",
doi = "10.1007/BF00173791",
language = "English (US)",
volume = "2",
pages = "79--84",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "1",

}

TY - JOUR

T1 - Tiazofurin

T2 - A new antitumor agent

AU - O'Dwyer, Peter J.

AU - Shoemaker, D. Dale

AU - Jayaram, Hiremagalur N.

AU - Johns, David G.

AU - Cooney, David A.

AU - Marsoni, Silvia

AU - Malspeis, Louis

AU - Plowman, Jacqueline

AU - Davignon, J. Paul

AU - Davis, Ruth D.

PY - 1984/3

Y1 - 1984/3

N2 - Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90% of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.

AB - Tiazofurin is an interesting drug now entering Phase I trials, with marked preclinical antitumor activity against P388 and L1210 leukemias, and the Lewis lung carcinoma. Schedule dependency favoring frequent administration has been noted. The drug has a novel mechanism of action, being metabolized to an inhibitory cofactor of inosine monophosphate dehydrogenase. Tiazofurin is widely distributed after i.v. administration exhibiting a triphasic pattern of plasma decay, with a terminal half-life of 3-16 h in the three species studied. Approximately 90% of the drug was excreted unchanged in the urine within 24 h. A significant potential for the slower release of intracellularly retained drug exists. Anticipated organ toxicities based on the studies described include myelotoxicity, hepatotoxicity and nephrotoxicity. These were mild and reversible at lower doses, and were not seen at levels corresponding to the starting doses in man. A potential for hyperuricemia exists; this should be easily controllable by the use of allopurinol, without compromising the drug's antitumor effect. Phase I trials under the sponsorship of the NCI are underway in a number of institutions.

KW - tiazofurin

UR - http://www.scopus.com/inward/record.url?scp=0021239408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021239408&partnerID=8YFLogxK

U2 - 10.1007/BF00173791

DO - 10.1007/BF00173791

M3 - Article

VL - 2

SP - 79

EP - 84

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 1

ER -