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| Type |
Poster Presentation |
| Area |
Medicinal Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
MEDI.P-667 |
| Subject |
Validation of HSP90 as a Target for Imaging of Cancer by MicorPET Imaging and Biodistribution of [18F]-labeled HSP90 Inhibitor on Triple Negative Breast Cancer Xenograft Model |
| Authors |
Julie Kang, Dong-Jo Chang*
Department of Pharmacy, Suncheon National University, Korea
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| Abstract |
HSP90 (Heat shock protein 90) is a molecular chaperone that assists other proteins, called client proteins, to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. Various oncogenic proteins including HIF-1α, receptor kinases containing ErbB2, MEK 1/2, CDKs, Src, Akt and Raf-1have been reported to be the client proteins of HSP90. Early HSP90 inhibitors such as gelanamycin (GA), 17-AAG and IPI-504 had been developed for the treatment of cancer in clinical trials, but failed to get in further development due to toxicity. Since the failure of early HSP90 inhibitors, diverse scaffolds of HSP90 inhibitors such as ganetespib, PU-H71 and NVP-AUY922 have been developed to get in clinic. Ganetespib, which has been discovered by Synta Inc, shows lower toxicity than previous HSP90 inhibitors containing GA, 17-AAG and other HSP90 inhibitor, and is currently under the phase III clinical trial. Ganetespib has been reported to show a tumor uptake over 20 times higher than normal tissues in clinical trial, which suggests that ganetespib can be used as a ligand targeting HSP90 for imaging of cancer. In this work, we synthesized [18F]-ganetespib derivative (1) with a triazole-PEG linker which was labeled by click chemistry, and assessed the tumor-specific uptake of the probe 1 by biodistribution and PET imaging in triple negative breast cancer (TNBC) orthotopic xenograft model induced by MDA-MB-231 breast cancer cells. |
| E-mail |
juliy19@naver.com |
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121st General Meeting of the KCS