IPI-504 Results of Phase 1 in GIST - ASCO 2008

Wagner, A.J., Morgan, J.A., Chugh, R., Rosen, L.S., George, S., Gordon, M.S., Blackstein, M.E., Butrynski, J., Devine, C.M., Van den Abbeele, A.D., Grayzel, D., Demetri, G.D. Results from Phase 1 Trial of IPI-504, a Novel Hsp90 Inhibitor, in Tyrosine Kinase Inhibitor-Resistant GIST and other Sarcomas. American Society of Clinical Oncology Annual Meeting, 2008.

IPI-504 Preliminary Results of Phase 1 in NSCLC - EORTC 2007

Sequist, L., Janne, P., Sweeney, J., Walker, J., Grayzel, D., Lynch, T. (2007) Phase 1/2 Trial of the Novel Hsp90 Inhibitor, IPI-504, in Patients with Relapsed and/or Refractory Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC) Stratified by EGFR Mutation Status. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, B79, 2007.

IPI-504 Preliminary Results of Phase 1 in GIST - ASCO 2007

Van den Abbeele, A.D., Yap, J. T., Grayzel, D. S., Walker, J., Demetri, G.D. Inhibition and flare patterns of metabolic response to the Heat Shock Protein 90 (Hsp90) inhibitor IPI-504 visualized by FDG-PET in patients with advanced gastrointestinal stromal tumors (GIST) resistant to tyrosine kinase inhibitor (TKI) therapy. American Society of Clinical Oncology Annual Meeting, 2007.

IPI-504 Preliminary Results of Phase 1 in GIST - ASCO 2007

Demetri, G.D., George, S., Morgan, J., Wagner, A., Quigley, M.T., Polson, K., Pokela, J., van den Abbeele, A., Chugh, R., Walker, J., Adams, J. and Grayzel, D. (2007) Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors (TKIs) in metastatic gist: Updated results of a phase I trial. American Society of Clinical Oncology Annual Meeting, 2007.

IPI-504 - PNAS 2007

Sydor, J.R., Normant, E., Pien, C.S., Porter, J.R., Ge, J., Grenier, L., Pak, R.H., Ali, J.A., Dembski, M.S., Hudak, J., Patterson, J., Penders, C., Pink, M., Read, M.A., Sang, J., Woodward, C., Zhang, Y., Grayzel, D.S., Wright, J., Barrett, J.A., Palombella, V.J., Adams, J. and Tong, J.K. Development of 17-allylamino-17-demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90. PNAS 2006;103;17408-17413.

IPI-504 - DOI 2007

J. Patterson, V. Palombella, C. Fritz, E. Normant. IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol. DOI 10.2007/soo280-007-0546-0.

IPI-504 - Journal of Medicinal Chemistry 2006

Ge, J., Normant, E., Porter, J.R., Ali, J.A., Dembski, M.S., Gao, Y., Georges, A.T., Grenier, L., Pak, R.H., Patterson, J., Sydor, J.R., Tibbitts, T.T., Tong, J.K., Adams, J. and Palombella, V.J. Design, Synthesis, and Biological Evaluation of Hydroquinone Derivatives of 17-Amino-17-demethoxygeldanamycin as Potent, Water-Soluble Inhibitors of Hsp90. J. Med. Chem. 2006, 49, 4606-4615.

IPI-926 Preclinical Results

M. Pink, J. Proctor, K. Briggs, J. MacDougall, N. Whitebread, M. R. Tremblay, M. Grogan, V. Palombella, A. Castro, J. Adams, M. Read, I. M. Corcoran-Schwartz, T. Harcke, C. G. Eberhart, D. N. Watkins, J. Sydor. Activity of IPI-926, a potent HH pathway inhibitor, in a novel model of medulloblastoma derived from Ptch/HIC +/- mice. American Association for Cancer Research, 1588, 2008.

V. Travaglione, C. Peacock, J. MacDougall, K. McGovern, J. Cushing, L. Yu, M. Trudeau, V. Palombella, J. Adams, J. Hierman, J. Rhodes, W. Devereux, D. Watkins. A novel Hh pathway inhibitor, IPI-926, delays recurrence post-chemotherapy in a primary human SCLC xenograft model. American Association for Cancer Research, 4611, 2008.

Kerrie Faia, Everton Mandley, Suzy Dembski, Christine Pien, John MacDougall, Jennifer Hoyt, Matthew Campbell, Grace Lin, Priscilla Lo, Margaret Read and Karen McGovern. Depilation Induced Anagen as a Model to Study Hedgehog Pathway Antagonist IPI-926 Implications for Biomarker Development. American Association for Cancer Research, 2827, 2008.

M.Tremblay, K. McGovern, M. Nevalainen, S. Nair, J. Porter, M. Behnke, L.Yu, L. Grenier, M. Campbell, J. Cushing, Z. El-Assi, A. Castro, M. Curtis, M. Foley, J. Wright, J. Tong, V. Palombella, J. Adams. Synthesis of novel, chemically stable D-homo-cyclopamine analogs via a cyclopropanation/ring-expansion sequence. GRC, 2007.

 

Bcl-2 Preclinical Results

N. Hafeez, A. Wylie, J. Conley, K. White, D. Mann, V. Palombella, C. Fritz. Inhibitors of Bcl-2 have a unique profile of inducing the apoptotic cascade downstream of the mitochondria. Keystone Symposia, 148, 2007.

Tillotson, B., Mann, D., Brophy, E., Ali, J., Palombella, V. and Fritz, C. A Novel Binding Assay for Native Bcl-2 on Intact Mitochondria. American Association for Cancer Research Annual Meeting, 3628, 2007.

Wylie, A., Hafeez, N., Conley, J., White, K., Mann, D., Palombella, V., and Fritz, C. (2007) A Unique Apoptosis Marker Profile for Antagonists of Bcl-2. American Association for Cancer Research Annual Meeting, 5163, 2007.

Peng, C., Brain, J., Hu, Y., Goodrich, A., Kong, L., Grayzel, D., Pak, R., Read, M. and Li, S. Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I–induced leukemia and suppresses leukemic stem cells. Blood, 15 July 2007,Volume 110, Number 2