Initial testing of VNP40101M (Cloretazine®) by the pediatric preclinical testing program

Stephen T. Keir, Christopher L. Morton, Catherine Billups, Malcolm A. Smith, Peter J. Houghton, Sridharan Gururangan

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

VNP40101M is a novel alkylating agent that yields two reactive compounds (a chloroethylating species and methylisocyanate) and has demonstrated activity against a wide spectrum of tumor xenografts. VNP40101M was tested against an in vivo panel of five pediatric brain tumor xenografts at a dose of 18 mg/kg/day administered for 5 days. O-6-methylguanine-DNA methyltransferase (MGMT) levels of xenografts were assessed by Western blot analysis. Only one xenograft (GBM2), which lacked detectable MGMT expression, demonstrated an objective response to VNP40101M. VNP4010M antitumor activity was observed only in the absence of MGMT expression, with resistance to VNP4010M seen even with low MGMT expression.

Original languageEnglish (US)
Pages (from-to)439-441
Number of pages3
JournalPediatric Blood and Cancer
Volume51
Issue number3
DOIs
StatePublished - Sep 2008
Externally publishedYes

Keywords

  • Developmental therapeutics
  • Preclinical testing
  • VNP40101M

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology

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