Retaspimycin hydrochloride (IPI-504): A novel heat shock protein inhibitor as an anticancer agent

Expert Opinion on Investigational Drugs

Volumn 18, Issue 9, 2009, Pages 1375-1383

  Hanson, Britt Erika ^a   Vesole, David H ^a  

^a LOYOLA UNIVERSITY CHICAGO   (United States)

Author keywords

Cancer; Heat shock protein; IPI 504; Non small cell lung cancer; NSCLC; Retaspimycin

Indexed keywords

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; DOCETAXEL; GELDANAMYCIN; HEAT SHOCK PROTEIN; HEAT SHOCK PROTEIN 90; IMATINIB; LY 24009; PACLITAXEL; PLACEBO; PROTEIN INHIBITOR; TANESPIMYCIN; TANESPIMYCIN HYDROQUINONE; TRASTUZUMAB; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; B CELL LYMPHOMA; BRAIN HEMORRHAGE; BREAST CANCER; CANCER REGRESSION; CLINICAL TRIAL; DIARRHEA; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG FATALITY; DRUG STRUCTURE; DRUG TOLERABILITY; FATIGUE; GASTROINTESTINAL STROMAL TUMOR; GASTROINTESTINAL TUMOR; HEADACHE; HUMAN; HYPERGLYCEMIA; KETOACIDOSIS; LEUKEMIA; LIVER TOXICITY; LUNG NON SMALL CELL CANCER; MANTLE CELL LYMPHOMA; MELANOMA; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NONHUMAN; PANCREAS CANCER; PHENOTYPE; PROSTATE CANCER; REVIEW; SIDE EFFECT;

ANTINEOPLASTIC AGENTS; BENZOQUINONES; CLINICAL TRIALS AS TOPIC; HSP90 HEAT-SHOCK PROTEINS; HUMANS; LACTAMS, MACROCYCLIC; MOLECULAR STRUCTURE; NEOPLASMS; TREATMENT OUTCOME;

EID: 68849101479     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543780903158934     Document Type: Review

References (28)

1. Neckers L. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 2002;8(4 Suppl):S55-61
2. Bishop SC, Burlison JA, Blagg BS. Hsp90: a novel target for the disruption of multiple signaling cascades. Curr Cancer Drug Targets 2007;7:369-88
3. Simms-Waldip T, Rodriguz-Gonzalez A, Lin T, et al. The aggresome pathway as a target for therapy in hematologic malignancies. Mol Gen Met 2008;94:283-6
4. Amolins MW, Blagg BS. Natural product inhibitors of Hsp90: potential leads for drug discovery. Med Chem 2009;9(2):140-52
5. Sydor JR, Normant E, Pien CS, et al. Development of 17-allylamino-17- demethoxygeldanamycin hydroquinone hydrochloride (IPI-504), an anti-cancer agent directed against Hsp90. PNAS 2006;103(46):17408-13
6. Takimoto CH, Diggikar S. Heat shock protein and proteasome targeting agents. Hematol Oncol Clin North Am 2002;16:1269-85
7. Taldone T, Sun W, Chiosis G. Discovery and development of heat shock protein 90 inhibitors. Bioorg Med Chem 2009;17:2225-35
8. Wandinger SK, Richter K, Buchner J. The Hsp90 chaperone machinery. J Biol Chem 2008;283(27):18473-7
9. Ferrarini M, Heltai S, Zocchi MR, et al. Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer 1992;51:613-19
10. Grenert JP, Sullivan WP, Fadden P, et al. The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem 1997;272:23843-50
11. Callahan MK, Garg M, Srivastava PK. Heat-shock protein 90 associates with N-terminal extended peptides and is required for direct and indirect antigen presentation. PNAS 2008;105:1662-7
12. Kunisawa J, Shastri N. Hsp90a chaperones large C-terminally extended proteolytic intermediates in the MHC class I antigen processing pathway. Immunity 2006;24:523-34
13. Sequist L, Janne P, Sweeney J, et al. 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 2007: abstract #B79
14. Sequist L, Natale R, Gettinger S, et al. Interim Results From a Phase 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. ASCO Meeting Abstract 2009;27:8073
15. Wagner AJ, Morgan JA, Chugh R, et al. Results from Phase 1 Trial of IPI-504, a Novel HSP90 Inhibitor, in Tyrosine Kinase Inhibitor-Resistant GIST and other Sarcomas. ASCO Annual Meeting 2008
16. Johnston A, Allaire M. Infinity Halts RING Trial in Advanced Gastrointestinal Stromal Tumors. Available from: http://investor.ipi.com/ releasedetail. cfm?ReleaseID=377328
17. Mitsiades CS, Mitsiades M, Rooney M, et al. IPI-504: a novel hsp90 inhibitor with in vitro and in vivo anti-tumor activity. Blood 2004;104:abstract 2403
18. Patterson J, Palombella VJ, Fritz C, et al. IPI-504, a novel and soluble HSP-90 inhibitor, blocks the unfolded protein response in multiple myeloma cells. Cancer Chemother Pharmacol 2008;61:923-32
19. Palombella VJ, Emmanuel N, Janid A, et al. Anti-tumor activity of IPI-504, a novel Hsp90 inhibitor in multiple myeloma. Blood 2004;104:abstract 4922
20. Siegel D, Jagannath S, Mazumder A, et al. Update on Phase I clinical trial of IPI-504, a novel, water-soluble Hsp90 inhibitor, in patients with relapsed/refractory multiple myeloma (MM). Blood 2006;108:abstract 3579
21. Oh WK, Stadler WM, Srinivas S, et al. A single arm phase II trial of IPI-504 in patients with castration resistant prostate cancer (CRPC). Genitourinary Cancers Symposium 2009
22. Drysdale MJ, Brough PA, Massey A. Targeting Hsp90 for the treatment of cancer. Curr Opin Drug Discov Dev 2006;9:483-95
23. Abramson JS, Chen W, Juszczynski P, et al. The heat shock protein 90 inhibitor IPI-504 induces apoptosis of AKT-dependent diffuse large B-cell lymphomas. Br J Haematol 2009;144(3):358-66
24. Roue G, Perez-Galan P, Lopez-Guerra M, et al. The novel HSP90 inhibitor IPI-504 synergizes with bortezomib in mantle cell lymphoma cells by targeting both NF-kappaB signaling and unfolded protein response and leading to increased mitochondrial apoptosis. Blood 2007;110:abstract 1601
25. Peng C, Brain J, Goodrich A. Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I-induced leukemia and suppresses leukemic cells. Blood 2007;110(2):678-85
26. Song D, Chaerkady R, Choon Tan A, et al. Antitumor activity and molecular effects of the novel heat shock protein inhibitor, IPI-504, in pancreatic cancer. Mol Cancer Ther 2008;7:3275
27. Riely GJ, Stoller R, Egorin M, et al. Interim Results From a Phase Ib Trial of IPI-504 (retaspimycin hydrochloride), a Novel Hsp90 Inhibitor, in Combination with Docetaxel. ASCO Meeting Abstracts 2009;27:3547
28. Richardson PG, Chanan-Kan A, Lonial S, et al. Tanespimycin (T) + Bortezomib (BZ)-in Multiple Myeloma (MM): confirmation of the recommended dose using a novel formulation. 2007 ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 2007;25(18S)(June 20 Suppl):3532