Combined alkylation and histone deacetylase inhibition with EDO-S101 has significant therapeutic activity against brain tumors in preclinical models

Yushi Qiu, Zhimin Li, John A III Copland, Thomas Mehrling, Han W Tun

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

There is a clear unmet need for novel therapeutic agents for management of primary and secondary brain tumors. Novel therapeutic agents with excellent central nervous system (CNS) penetration and therapeutic activity are urgently needed. EDO-S101 is a novel alkylating and histone deacetylase inhibiting agent created by covalent fusion of bendamustine and vorinostat. We used murine models to perform CNS pharmacokinetic analysis and preclinical therapeutic evaluation of EDO-S101 for CNS lymphoma, metastatic triple-negative breast cancer of the brain, and glioblastoma multiforme. EDO-S101 has excellent CNS penetration of 13.8% and 16.5% by intravenous infusion and bolus administration respectively. It shows promising therapeutic activity against CNS lymphoma, metastatic triple-negative breast cancer of the brain, and glioblastoma multiforme with significant prolongation of survival compared to no-treatment controls. Therapeutic activity was higher with IV infusion compared to IV bolus. It should be evaluated further for therapeutic use in brain tumors.

Original languageEnglish (US)
Pages (from-to)28155-28164
Number of pages10
JournalOncotarget
Volume9
Issue number46
DOIs
StatePublished - Jun 15 2018

Fingerprint

Histone Deacetylases
Alkylation
Brain Neoplasms
Central Nervous System
Triple Negative Breast Neoplasms
Glioblastoma
Therapeutics
Lymphoma
Therapeutic Uses
EDO-S101
Intravenous Infusions
Pharmacokinetics

Keywords

  • Brain tumors
  • CNS lymphoma
  • EDO-S101
  • Glioblastoma multiforme
  • Metastatic breast cancer of the brain

ASJC Scopus subject areas

  • Oncology

Cite this

Combined alkylation and histone deacetylase inhibition with EDO-S101 has significant therapeutic activity against brain tumors in preclinical models. / Qiu, Yushi; Li, Zhimin; Copland, John A III; Mehrling, Thomas; Tun, Han W.

In: Oncotarget, Vol. 9, No. 46, 15.06.2018, p. 28155-28164.

Research output: Contribution to journalArticle

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