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Tubulin polymerization inhibitor

IPC-003 was found out as a highly efficacious compound in the process of our strategic screening system for discovery of anti-cancer agents. This compound showed a strong growth inhibitory effect on cultured tumor cell lines in vitro and on human colorectal cancer, LS174T cells (xenograft model) in vivo, but its mechanism of action (MOA) had been unclear for a period of time. Cell and molecular biological approaches and subsequent careful consideration on the results revealed that MOA of IPC-003 is an inhibition of tubulin polymerization. We evaluated effects of IPC-003 mainly on leukemic cells in vitro and in vivo, and obtained the following results:

  • IPC-003 inhibited proliferation of both lymphocytic and myelocytic leukemia cells with high potency.
  • In vitro analysis revealed that IPC-003 can induce intrinsic cell death/cell cycle arrest and differentiation in myelocytic leukemia cells.
  • IPC-003 strongly suppressed the growth of HL-60 cells in nude mice both when administered prophylactically and therapeutically.
  • It showed substantially no kinase inhibition.

We believe that IPC-003 has a potential to contribute to the treatment for acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) not only by the combination therapy with current chemotherapeutic agents but also the monotherapy based on the data indicated above and good safety profile.