Current status of pyrazoloacridine as an anticancer agent

Research output: Contribution to journalReview article

42 Citations (Scopus)

Abstract

Pyrazoloacridine (PZA) is the first of a new class of rationally synthesized acridine derivatives to undergo clinical testing as an anticancer agent. Recent studies suggest that PZA might be a dual inhibitor of DNA topoisomerase I and DNA topoisomerase II that exerts its effects by diminishing the formation of topoisomerase-DNA adducts. Consistent with this unique mechanism of action, PZA exhibits broad spectrum antitumor activity in preclinical models in vivo. In addition, this agent displays several unique properties including solid tumor selectivity, activity against hypoxic cells, and cytotoxicity in noncycling cells. PZA also retains full activity against cells that are resistant to other agents on the basis of overexpression of P-glycoprotein or the multidrug resistance-associated protein (MRP). PZA has been studied in phase I trials in adults and children, and is currently undergoing broad phase II trials in a number of tumor types. No significant anti-tumor activity has been seen in gastrointestinal malignancies and prostate cancer. Results from ongoing or recently completed trials are awaited before the utility of this agent in our current armamentarium can be defined. Because of its unique properties, combination studies with other antineoplastic agents are warranted.

Original languageEnglish (US)
Pages (from-to)43-48
Number of pages6
JournalInvestigational New Drugs
Volume17
Issue number1
DOIs
StatePublished - Oct 6 1999

Fingerprint

NSC 366140
Antineoplastic Agents
Neoplasms
Topoisomerase I Inhibitors
Acridines
Multidrug Resistance-Associated Proteins
Type II DNA Topoisomerase
Gastrointestinal Neoplasms
DNA Adducts
P-Glycoprotein
Prostatic Neoplasms

Keywords

  • Acridine derivative
  • DNA intercalation
  • Pyrazoloacridine
  • Topoisomerases

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Current status of pyrazoloacridine as an anticancer agent. / Adjei, Alex.

In: Investigational New Drugs, Vol. 17, No. 1, 06.10.1999, p. 43-48.

Research output: Contribution to journalReview article

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