Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity - PubMed (original) (raw)
Review
Geldanamycin as a potential anti-cancer agent: its molecular target and biochemical activity
L Neckers et al. Invest New Drugs. 1999.
Abstract
Heat shock protein 90 is one of the most abundant cellular proteins. Although its functions are still being characterized, it appears to serve as a chaperone for a growing list of cell signaling proteins, including many tyrosine and serine/threonine kinases, involved in proliferation and/or survival. The benzoquinone ansamycin geldanamycin has been shown to bind to Hsp90 and to specifically inhibit this chaperone's function, resulting in client protein destabilization. Its ability to simultaneously stimulate depletion of multiple oncogenic proteins suggests that geldanamycin, or other molecules capable of targeting Hsp90 in cancer cells, may be of clinical benefit.
Similar articles
- The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin.
Schulte TW, Neckers LM. Schulte TW, et al. Cancer Chemother Pharmacol. 1998;42(4):273-9. doi: 10.1007/s002800050817. Cancer Chemother Pharmacol. 1998. PMID: 9744771 - Hsp90 inhibitor geldanamycin and its derivatives as novel cancer chemotherapeutic agents.
Miyata Y. Miyata Y. Curr Pharm Des. 2005;11(9):1131-8. doi: 10.2174/1381612053507585. Curr Pharm Des. 2005. PMID: 15853661 Review. - [Molecular chaperone HSP90 as a novel target for cancer chemotherapy].
Miyata Y. Miyata Y. Nihon Yakurigaku Zasshi. 2003 Jan;121(1):33-42. doi: 10.1254/fpj.121.33. Nihon Yakurigaku Zasshi. 2003. PMID: 12617036 Review. Japanese. - Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin.
Roe SM, Prodromou C, O'Brien R, Ladbury JE, Piper PW, Pearl LH. Roe SM, et al. J Med Chem. 1999 Jan 28;42(2):260-6. doi: 10.1021/jm980403y. J Med Chem. 1999. PMID: 9925731
Cited by
- Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94.
Ansa-Addo EA, Thaxton J, Hong F, Wu BX, Zhang Y, Fugle CW, Metelli A, Riesenberg B, Williams K, Gewirth DT, Chiosis G, Liu B, Li Z. Ansa-Addo EA, et al. Curr Top Med Chem. 2016;16(25):2765-78. doi: 10.2174/1568026616666160413141613. Curr Top Med Chem. 2016. PMID: 27072698 Free PMC article. Review. - Heat shock protein 90: biological functions, diseases, and therapeutic targets.
Wei H, Zhang Y, Jia Y, Chen X, Niu T, Chatterjee A, He P, Hou G. Wei H, et al. MedComm (2020). 2024 Jan 25;5(2):e470. doi: 10.1002/mco2.470. eCollection 2024 Feb. MedComm (2020). 2024. PMID: 38283176 Free PMC article. Review. - Different poses for ligand and chaperone in inhibitor-bound Hsp90 and GRP94: implications for paralog-specific drug design.
Immormino RM, Metzger LE 4th, Reardon PN, Dollins DE, Blagg BS, Gewirth DT. Immormino RM, et al. J Mol Biol. 2009 May 22;388(5):1033-42. doi: 10.1016/j.jmb.2009.03.071. Epub 2009 Apr 8. J Mol Biol. 2009. PMID: 19361515 Free PMC article. - The Hsp90 chaperone machinery regulates signaling by modulating ligand binding clefts.
Pratt WB, Morishima Y, Osawa Y. Pratt WB, et al. J Biol Chem. 2008 Aug 22;283(34):22885-9. doi: 10.1074/jbc.R800023200. Epub 2008 May 30. J Biol Chem. 2008. PMID: 18515355 Free PMC article. Review. No abstract available. - Translation initiation control by heme-regulated eukaryotic initiation factor 2alpha kinase in erythroid cells under cytoplasmic stresses.
Lu L, Han AP, Chen JJ. Lu L, et al. Mol Cell Biol. 2001 Dec;21(23):7971-80. doi: 10.1128/MCB.21.23.7971-7980.2001. Mol Cell Biol. 2001. PMID: 11689689 Free PMC article.
References
- J Biochem. 1994 Mar;115(3):486-92 - PubMed
- Biochem Mol Biol Int. 1995 Jan;35(1):95-102 - PubMed
- Lancet. 1993 Oct 23;342(8878):1024-5 - PubMed
- Genes Dev. 1996 Jun 15;10(12):1491-502 - PubMed
- Int J Oncol. 1993 Jun;2(6):1075-80 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources