Selective inhibition of HDAC6 against tumor formation and metastasis

SK 1503

SUMMARY OF INVENTION

Conventional chemotherapy is effective but has debilitating toxic side effects. MSK cell biologists and Columbia University chemists discovered a novel compound (SK1503) with the equivalent efficacy of chemotherapeutic agents, but without the typical adverse events. SK1503 is a potent hydroxamic acid-based small molecule, with the chemical structure of N-hydroxy-4-[(N(2-hydroxyethyl)-2- henylacetamido) methyl) benzamide)], or HPM. SK1503 selectively inhibits histone deacetylase 6 (HDAC6), which is associated with tumor formation and metastasis, in vivo and in vitro. SK1503 blocks the growth of normal and transformed cells but does not induce death of normal cells. The agent alone appears as effective as paclitaxel in anticancer activity in tumor-bearing mice. This is expected to lead to important anticancer activity.

ADVANTAGES

  • Although HPM blocks growth of normal and transformed cells, it does not induce death of normal cells
  • Selective inhibition of HDAC6 is expected to reduce or eliminate the often-severe side effects associated with non-selective HDAC inhibition
  • HPM alone is as effective as paclitaxel in anticancer activity in tumor-bearing mice

MARKET OPPORTUNITIES

As an indication of potential market size, HDAC inhibitors currently on the market include: Zolinza (vorinostat, Merck, 2006, CTCL), Farydak (panobinostat, Novartis, 2015, Multiple Myeloma), and Beleodaq (belinostat, Onxeo, 2015, PTCL and NHL). Other applicable indications include solid tumors, such as prostate cancer and neurodegenerative conditions.

According to the National Cancer Institute, approximately 21,700 Americans are diagnosed with multiple myeloma and 10,710 die from the disease annually. About 70,000 Americans are diagnosed with NHL and 19,000 die from NHL yearly. PTCL represents about 10-15% of NHL cases in North America.

STAGE OF DEVELOPMENT

Mouse model: androgen-dependent CWR22 human prostate cancer xenograft

The effects of HPB and paclitaxel were examined independently and in combination. Tumor suppression was observed in all treatment groups.

PATENT INFORMATION

Patent applications are filed and pending, including PCT/US2014/072234, and Europe, Canada, and Australia nationals

REFERENCES

Marks PA et. al, Proc Natl Acad Sci U S A. 2013 Sep 24;110(39): 15704-9.

LEAD INVESTIGATORS

Dr Paul Marks, a cell biologist by training, served as the President and CEO of MSK for 19 years.  In collaboration with Dr. Ronald Breslow of Columbia University, the team discovered and studied agents that selectively target histone deacetylases and cause transformed cell growth arrest, terminal differentiation, apoptosis, and/or cell death.

CONTACT INFORMATION

Sue Yao, MBA, MPH
Senior Licensing Manager
Tel: 646-888-1072
E-mail: yaox@mskcc.org

Stage of Development

Animal studies