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STA-9090 (Hsp90 INHIBITOR)
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Program Overview
STA-9090 is a novel, synthetic, small-molecule inhibitor of heat shock protein
90 (Hsp90), being developed for treating mutliple solid tumor and hematologic
cancers.
Hsp90 is a chaperone protein required for the proper folding and functioning of
other cellular proteins, particularly kinases. Many of these “client proteins”
of Hsp90 – such as AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, HIF-1a,
PDGFR, VEGFR – have been shown to be critical to cancer cell growth,
proliferation, and survival and are the targets of clinically validated cancer
drugs. In preclinical studies, inhibiting Hsp90 causes rapid degradation of
these client proteins and leads to cancer cell death. Because mutated kinases,
which no longer respond to kinase inhibitors, remain at least as dependent on
Hsp90 for their activity, inhibiting Hsp90 offers the potential for treating
cancers that have become resistant to drugs such as imatinib (Gleevec®),
erlotinib (Tarceva®), and sunitinib (Sutent®).
STA-9090 was discovered and developed internally at Synta and has a chemical
structure unrelated to the first-generation, ansamycin family of Hsp90
inhibitors such as 17-AAG. In preclinical studies, STA-9090 has shown potency
up to 100 times greater than the first-generation Hsp90 inhibitors as well as
activity against a wider range of kinases. In in vitro and in vivo
models, STA-9090 has shown potent activity against a wide range of cancer
types, including lung, prostate, colon, breast, gastric, pancreatic, melanoma
and certain hematologic cancers - as well as potent activity against cancers
resistant to Gleevec, Sutent, Tarceva, Sprycel, and 17-AAG.
Solid Tumor Cancers: Two dose-ranging Phase 1 clinical trials in solid
tumors are currently enrolling patients. The first trial is an open-label study
designed to identify the maximum tolerated dose of STA-9090 based on a
twice-per-week intravenous dosing schedule. The second trial evaluates a
once-per-week dosing schedule. The trials are designed to assess safety and
tolerability, as well as identify signals of biological activity, based on
biomarkers of Hsp90 inhibition, and clinical activity, based on tumor response.
Click here to get more information on our
Twice weekly trial.
Click here to get more information on our
Once weekly trial.
Blood Cancers: Two Phase 1/2 trials in hematologic malignancies are
currently enrolling patients. The first trial is an open-label study based on a
twice-weekly intravenous dosing schedule; the second trial evaluates
once-weekly administration.
Click here to get more information on our
Twice weekly trial.
Click here to get more information on our
Once weekly trial.
Phase 2 Trial in Non-Small Cell Lung Cancer: Synta is currently enrolling
patients in an open-label, multi-center, multi-cohort Phase 2 study designed to
identify the efficacy and safety of STA-9090 in patients with stage IIIB or IV
non-small cell lung cancer.
Click here to get more information on our
NSCLC trial.
Phase 2 Trial in Gastrointestinal Stromal Tumors: Synta is currently
enrolling patients in a multi-center, Phase 2 trial designed to identify
the efficacy and safety of STA-9090 in patients with metastatic or unresectable
GIST following failure of Gleevec® and Sutent®.
Click here to get more information on our
GIST trial.
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STA-9090 Presentations
| Meeting/Date
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Title |
Link |
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18th International Symposium on Targeted Anticancer Therapies (TAT)
March 5, 2010 - Bethesda, MD
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The Next Generation Hsp90 Inhibitor STA-9090,
Currently in Phase 2 Trials, Displays Potent in vitro and in vivo Activity
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Poster |
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10th Annual Targeted Therapies of Lung Cancer Meeting
February 25, 2010 - Santa Monica, CA
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STA-9090, A Potent 2nd Generation Hsp90 Inhibitor
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Presentation |
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Hematologic Malignancies: Bridging the Gap 2010
February 5-7, 2010 - Singapore City, Singapore
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Hsp90 Inhibitor STA-9090 Down-Regulates Expression of
Hsp90 Client Protein WT1 in Myeloid Leukemia Cells.
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Poster
Abstract |
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AACR-IASLC
Joint Conference on Molecular Origins of Lung Cancer
January 12, 2010 - Coronado, CA
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Synergy between the novel Hsp90 inhibitor STA-9090 and
taxanes in preclinical models of NSCLC.
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Poster |
AACR-NCI-EORTC
Molecular Targets and Cancer Therapeutics
November 18, 2009 - Boston, MA |
Pharmacodynamic analysis of the Hsp90 inhibitor
STA-9090 in a lung cancer xenograft model supports an infrequent dosing
schedule in the clinic.
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Poster
Abstract |
AACR-NCI-EORTC
Molecular Targets and Cancer Therapeutics
November 17, 2009 - Boston, MA |
In vitro and in vivo efficacy of the novel Hsp90
inhibitor STA-9090 and its synergy with paclitaxel.
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Poster
Abstract |
AACR-NCI-EORTC
Molecular Targets and Cancer Therapeutics
November 17, 2009 - Boston, MA |
Hsp90 inhibitor STA-9090 potently suppresses
heterogeneous KIT kinase-domain mutations responsible for gastrointestinal
stromal tumor progression during imatinib therapy.
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Poster
Abstract |
100th AACR Annual Meeting
April 21, 2009 - Denver, CO |
The novel Hsp90 inhibitor STA-9090 has potent
anticancer activity in in vitro and in vivo models of lung cancer.
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Poster
Abstract |
99th AACR Annual Meeting
April 14, 2008 - San Diego, CA |
The novel Hsp90 inhibitor STA-9090 exhibits activity
against Kit dependent and independent malignant mast cell tumors.
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Abstract |
99th AACR Annual Meeting
April 14, 2008 - San Diego, CA |
The novel Hsp90 inhibitor STA-12-1474 exhibits
biologic activity against canine osteosarcoma cell lines.
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Abstract |
STA-9090 Publications
| Meeting/Date
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Title/Author |
Link |
| International Journal of Cancer 2009.
125:2792-801. |
The novel Hsp90 inhibitor STA-1474 exhibits biologic
activity against osteosarcoma cell lines.
McCleese et al. |
Publication |
Experimental Hematology 2008.
36:1266-77. |
The novel Hsp90 inhibitor STA-9090 exhibits activity
against Kit-dependent and –independent malignant mast cell tumors.
Lin T, et al. |
Publication |
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General Hsp90 References
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Kim, YS, et al.: Update on Hsp90 Inhibitors in Clinical Trials. Curr Top Med
Chem. 2009; 9(15):1479-92.
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Mahalingam, D, et al.: Targeting Hsp90 for cancer therapy. Br J Cancer, 2009;
100(10):1523-9.
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Sawai, A, et al.: Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth
Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to
Paclitaxel. Cancer Res. 2008 Jan; 68(2):589-96.
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Solit, DB, Chiosis, G: Development and application of Hsp90 inhibitors. Drug
Discov Today. 2008; 13(1-2):38-43.
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Workman, P: Altered states: selectively drugging the Hsp90 cancer chaperone.
Trends Mol Med., 2004; 10(2):47-51.
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Xu, W, Neckers, L: Targeting the molecular chaperone heat shock protein 90
provides a multifaceted effect on diverse cell signaling pathways of cancer
cells. Clin Cancer Res. 2007; 13(6):1625-9.
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