The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked activity in in vivo and in vitro models of aggressive large B-cell lymphoma

Danielle Bongero, Luca Paoluzzi, Enrica Marchi, Kelly M. Zullo, Roberto Neisa, Yinghui Mao, Rafael Escandon, Ken Wood, Owen A. O'Connor

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

The kinesin spindle protein (KSP) is a mitotic protein essential for cell cycle control and motility. SB-743921 (hereafter SB-921) is an inhibitor that selectively targets the ATP-binding domain of the KSP. The preclinical activity of SB-921 was evaluated in models of diffuse large B-cell lymphoma (DLBCL). The cytotoxicity of SB-921 was evaluated in a series of germinal center (GC-DLBCL) and post-germinal center (ABC-DLBCL) DLBCL cell lines and a murine lymphoma xenograft model. GC-DLBCL lines generally demonstrated greater sensitivity to SB-921. IC50 values ranged between 1 nM and 900 nM for GC-DLBCL compared to 1 nM to 10 M for ABC lines. SB-921 demonstrated marked activity in a xenograft model of Ly-1 (GC-DLBCL). While SB-921 was relatively more active in GC derived cell lines, ABC-derived lines still underwent apoptosis at higher concentrations. These results demonstrate that SB-921 inhibits proliferation and induces apoptosis in both GC-DLBCL and ABC-DLBCL.

Original languageEnglish (US)
Pages (from-to)2945-2952
Number of pages8
JournalLeukemia and Lymphoma
Volume56
Issue number10
DOIs
Publication statusPublished - Oct 3 2015
Externally publishedYes

    Fingerprint

Keywords

  • Diffuse large B-cell lymphoma non-Hodgkin lymphoma
  • kinesin spindle protein
  • SB-743921

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this