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Updated: Aug 13, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Initial testing (stage 1) of BAL101553, a novel tubulin binding agent, by the pediatric preclinical testing program
E Anders Kolb1, Richard Gorlick, Stephen T Keir
1Nemours/A.I. duPont Hospital for Children, Wilmington, Delaware.
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.
Insights
BAL101553, a prodrug of BAL27862, halts cancer cell growth by disrupting microtubules. In preclinical models, it showed significant efficacy in solid tumors and certain leukemias, though objective responses were not observed.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- BAL101553 is a water-soluble prodrug designed to deliver BAL27862, a potent anti-cancer agent.
- BAL27862 functions by disrupting the microtubule network, a critical component of cell division.
Purpose of the Study:
- To evaluate the anti-cancer efficacy of BAL101553 and its active metabolite BAL27862.
- To characterize the in vitro and in vivo activity of BAL101553 against various cancer models.
Main Methods:
- In vitro assays were performed to determine the IC50 values of BAL27862 against cancer cell lines.
- In vivo studies involved administering BAL101553 to solid tumor and acute lymphoblastic leukemia (ALL) xenografts in mice.
Main Results:
- BAL27862 exhibited potent in vitro activity with a median relative IC50 of 13.8 nM.
- BAL101553 demonstrated significant differences in event-free survival (EFS) in 53% of solid tumor xenografts and 67% of ALL xenografts compared to controls.
- No objective responses were observed in the xenograft models.
Conclusions:
- BAL101553 is a promising anti-cancer agent with potent in vitro activity and preclinical efficacy in disrupting tumor growth.
- The distinct mechanism of action of BAL27862 differentiates it from existing therapies like vincristine.
- Further investigation is warranted to explore the therapeutic potential of BAL101553, despite the absence of objective responses in current xenograft models.
