ASCO GI 2010

Demetri, G., Le Cesne, A., von Mohren, M., Chmielowski, B., Chow, W., Rodenas, E., McKee, K., Grayzel, D., Kang, Y. Final results from a Phase III study of IPI-504 (retaspimycin hydrochloride) versus placebo in patients with gastrointestinal stromal tumors (GIST) following failure of tyrosine kinase inhibitor (TKI) therapies. American Society for Clinical Oncology Gastrointestinal Cancers Symposium, 2010.

ASCO 2009

Sequist, L., Natale, R., Gettinger, S., Senzer, N., Martins, R., Lilenbaum, R., Gray, J., Janne, P., Samuel, T., Harper, H., Walker, J., Sweeney, J., Ross, R., Grayzel, D., Lynch, T. Interim Results from a Phaes 2 Trial of IPI-504 (retaspimycin hydrochloride), a Novel Hsp90 Inhibitor, in Patients with Relapsed and/or Refractory Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC) Stratified by EGFR Mutation Status. American Society for Clinical Oncology, 2009.

Riely, G.J., Stoller, R., Egorin, M., Solit, D., Gabrail, N., Dunbar, J., Savage, A., Walker, J., Grayzel, D., Ross, R., Weiss, G.J.. Interim Results from a Phase 1b Trial of IPI-504 (retaspimycin hydrochloride), a Novel Hsp90 Inhibitor, in Combination with Docetaxel. American Society for Clinical Oncology, 2009.

AACR 2009

Scaltriti, M., Guzman, M., Normant, E., Jimenez, J., Prudkin, L., Aura, C., Baselga, J. The Hsp90 inhibitor IPI-504 inhibits proliferation and tumor growth of HER2 overexpressing breast cancer cells with acquired trastuzumab resistance. American Association for Cancer Research, 2009.

Floris, G., Debiec-Rychter, M., Sciot, R., Stefan, C., Wozniak, A., Machiels, K., Normant, E., Schoffski, P. Efficacy of IPI-504 "a novelinhibitor of heat shock protein 90" in a preclinical mouse model of gastrointestinal stromal tumor (GIST). American Association for Cancer Research, 2009.

Tillotson, B., Coco, J., Whitebread, N., West, K., Slocum, K., Thomas, B., Ge, J., Ali, J., Normant, E., Hoyt, J., MacDougall, J., Sydor., J., Palombella, V., Adams, J., Fritz, C. A novel pharmacodynamic assay to measure Hsp90 target occupancy by the small molecule inhibitors IPI-504 and IPI-493 in tumors. American Association for Cancer Research, 2009.

Normant, E., Douglas, M., Lim, A.R., West, K., Pink., M.M., Ge, J., Biggs, K., Porter, J.R., Wylie, A., Tibbitts, T., Curtis, M., Palombella, V., Adams, J., Fritz., C. The anti-proliferative activity of the Hsp90 inhibitor is not dependent on NQO1 oxidoreductase activity in vivo. American Association for Cancer Research, 2009.

ASCO GU 2009

Oh, W.K., Stadler, W.M., Srinivas, S., Chu, F., Bubley, G., Quigley, M., Goddard, J., Dunbar, J., Grayzel, D., Ross, R.W. A single arm Phase 2 trial of IPI-504 in patients with castration-resistant prostate cancer. American Society of Clinical Oncology Genitourinary Cancer Symposium, 2009.

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.

EORTC 2008

Fritz, C., Ge, J., Hafez, N., Tillotson, B., Depew, K., Coco, J., Basuki, J., Lim, A., Patterson, J., Porter, J., Palombella, V., and Normant, E. Comparison of the cellular and biochemical properties of ansamycin and non-ansamycin based Hsp90 inhibitors. EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics,” 2008.

EORTC 2007

Sequist, L., Janne, P., Sweeney, J., Walker, J., Grayzel, D., Lynch, T. 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.

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.

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.

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.

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.

Blood 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

Journal of Medicinal Chemistry 2006

Lee., J., Grenier, L., Holson, E., Slocum, K., Coco, J., Ge, J., Normant, E., Hoyt, J., Lim, A., Cushing, J., Sydor, J., and Wright, J. IPI-493, a potent, orally bioavailable Hsp90 inhibitor of the ansamycin class. EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics,” 2008.

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.

Journal of Medicinal Chemistry June 2009

Tremblay, Martin, et al. Discovery of a Potent and Orally Active Hedgehog Pathway (IPI-926). Journal of Medicinal Chemistry, 52(14).

Science 2009

Olive, Kenneth P., et al. Inhibition of Hedgehog Signaling Enhances Delivery of Chemotherapy in a Mouse Model of Pancreatic Cancer. Science, 2009. Available from Sciencexpress. http://www.scienceexpress.org.

AACR 2009

Tremblay, M.R., Lescarbeau, A., Grogan, M.J., Tan, E., Lin, G., Behnke, M.L., Austad, B.C., Yu, L.C., Trudeau, M., Grenier, L., Lo, P., Nair, S.J., Hagel, M., White, K., Manna, J., Alvarez-Diez, T., Hoyt, J., Sydor, J.R., Pink, M., MacDougall, J., Campbell, M.J., McGovern, K., Read, M., Palombella, V.J., Adams, J., Castro, A.C. The Hedgehog Pathway in Cancer: The Discovery of IPI-926. American Association for Cancer Research, 2009.

Peacock, C., Martelotto, L.G., Travaglione, V., McGovern, K., Read., M., Berman, D.M., Matsui, W., Watkins, D.N. Visualization of SMOOTHENED activation supports an essential role for Hedgehog signaling in the regulation of self-renewal in small cell lung cancer. American Association for Cancer Research, 2009.

Villavicencia, E., Khanna, P., Ditzler, S., Pullar, B., Hansen, S., Read, M., Faia, K., Hatton, B., Knoblaugh, S., Randolph-Habecker, J., LeBlanc, M., Shaw, D., Friedman, S., McGovern, K., Olson, J. Activity of the Hh pathway inhibitor IPI-926 in a mouse model of medulloblastoma. American Association for Cancer Research, 2009.

Travaglione, V., Faia, K., Conley, J., Frank, N., Proctor, J., White, K., Osswalt, M., Deyneko, I., MacDougall, J., Peacock, C., Watkins, D.N., McGovern, K., Read., M. Induction of tumor-derived hedgehog ligand by chemotherapy. American Association for Cancer Research, 2009.

ACS Annual Meeting 2009

Tremblay, M.R., Lescarbeau, A., Grogran, M.J., Tan, E., Lin, G., Behnke., M.L., Austad, B.C., Yu, L.C., Trudeau, M., Grenier, L., Lo, P., Nair, S.J., Hagel, K., White, K., Manna, J., Alvarez-Diez, T., Hoyt, J., Sydor, J.R., Pink, M., MacDougall, J., Campbell, M.J., McGovern, K., Read, M.A., Palombella, V., J., Adams, J., Castro, A.C. Discovery of IPI-926, a Semi-Synthetic Clinical Candidate that Targets the Hedgehog Pathway. American Chemical Society Meeting, 2009.

Tremblay, M.R., Lescarbeau, A., Grogran, M.J.,, Tan, E., White, K., McGovern, K., Castro, A.C. Synthesis and Structure Activity Relationship of D-homo Cyclopamine Analogs: 3-Substituted Analogs. American Chemical Society Meeting, 2009.

Grogan, M.J., Lescarbeau, A., Tremblay, M.R., Lin, G., Hagel, M., McGovern, K., Castro, A.C. Synthesis and Structure Activity of D-home Cyclopamine Analogs: A-ring fused Heterocyclic Analogs. American Chemical Society Meeting, 2009.

Lescarbeau, A., Gorgan, M.J., Tremblay, M.R., Nair., S.J., Conley, J., McGovern, K., Castro, A.C. Synthesis and Structure Activity Relationship of D-homo Cyclopamine Hedgehog Antagonists: 7-Membered A-ring Lactam Analogs. American Chemical Society Meeting, 2009.

SGO Annual Meeting 2009

Growdon, W.M., McCann, C.R., Curley, M., Friel A.M., Mandley, E., Ferguson, J., Foster, R., MacDougal, J., Rueda, B.R. Hedgehog pathway inhibitor cyclopamine suppresses Gli1 expression and inhibits serous ovarian cancer xenograft growth. Society of Gynecologic Oncologists Annual Meeting on Women's Cancer, 2009.

EORTC 2008

Traviglione, V., Deyneko, I., Oaks, Z., Pink, M., Proctor, J., Mandley, E., Gu, L., Osswalt, M., Read, M., Sydor, J., McGovern, K., Palombella, V., MacDougall, J. Activity of IPI-926, a novel inhibitor of the Hh pathway, in subcutaneous and orthotopically implanted xenograft tumors that express SHh ligand. EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics,” 2008.

AACR 2008

Pink, M., Proctor, J., Briggs, K., MacDougall, J., Whitebread, N., Tremblay, M.R., Grogan, M., Palombella, V., Castro, A., Adams, J., Read, M., Corcoran-Schwartz, I.M., Harcke, T., Eberhart, C.G., Watkins, D. N., Sydor, J.. 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.

Travaglione, V., Peacock, C., MacDougall, J., McGovern, K., Cushing, J., Yu, L., Trudeau, M., Palombella, V., Adams, J., Hierman, J., Rhodes, J., Devereux, W., Watkins, D.N. 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.

Faia, K., Mandley, E., Dembski, S., Pien, C., MacDougall, J., Hoyt, J., Campbell, M., Lin, G., Lo, P., Read, M., McGovern, K. Depilation Induced Anagen as a Model to Study Hedgehog Pathway Antagonist IPI-926 Implications for Biomarker Development. American Association for Cancer Research, 2827, 2008.

GRC 2007

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

Keystone Symposium 2008

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.

AACR 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.