title: Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program.
abstract: BAL101553 is a highly water soluble prodrug of BAL27862 that arrests tumor cell proliferation and induces cell death in cancer cells through disruption of the microtubule network. In vitro BAL27862 demonstrated potent activity, with the median relative IC50 (rIC50 ) of 13.8 nM (range 5.4-25.2 nM). The in vitro activity of BAL27862 against the PPTP cell lines is distinctive from that previously described for vincristine. BAL101553 induced significant differences in EFS distribution compared to control in 16 of 30 (53%) solid tumor xenografts and in two of four (67%) of the evaluable ALL xenografts. No objective responses were observed.
authors.affiliation: Nemours/A.I. duPont Hospital for Children, Wilmington, Delaware.
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Keir
authors.forename: John M
authors.initials: JM
authors.lastname: Maris
authors.forename: Min H
authors.initials: MH
authors.lastname: Kang
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Richard B
authors.initials: RB
authors.lastname: Lock
authors.forename: Hernan
authors.initials: H
authors.lastname: Carol
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wu
authors.forename: Raushan T
authors.initials: RT
authors.lastname: Kurmasheva
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houghton
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D010069:Oxadiazoles / Q000627:therapeutic use*; D050257:Tubulin Modulators / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001562:Benzimidazoles; D010069:Oxadiazoles; D050257:Tubulin Modulators; C000599741:lisavanbulin
keywords: developmental therapeutics; microtubule-binding agents; preclinical testing; vascular-disrupting agents