- Radiosynthesis, biological evaluation and preliminary microPET study of 18F-labeled 5-resorcinolic triazolone derivative based on ganetespib targeting HSP90
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Heat-shock protein 90 (HSP90) is a molecular chaperone that activates oncogenic transformation in several solid tumors, including lung and breast cancers. Ganetespib, a most promising candidate among several HSP90 inhibitors under clinical trials, has entered Phase III clinical trials for cancer therapy. Despite numerous evidences validating HSP90 as a target of anticancer, there are few studies on PET agents targeting oncogenic HSP90. In this study, we synthesized and biologically evaluated a novel 18F-labeled 5-resorcinolic triazolone derivative (1, [18F]PTP-Ganetespib) based on ganetespib. [18F]PTP-Ganetespib was labeled by click chemistry of Ganetespib-PEG-Alkyne (10) and [18F]PEG-N3 (11) with 37.3 ± 5.11% of radiochemical yield and 99.7 ± 0.09% of radiochemical purity. [18F]PTP-Ganetespib showed proper LogP (0.96 ± 0.06) and good stability in human serum over 97% for 2 h. [18F]PTP-Ganetespib showed high uptakes in breast cancer cells containing triple negative breast cancer (TNBC) MDA-MB-231 and Her2-negative MCF-7 cells, which are target breast cancer cell lines of HSP90 inhibitor, ganetespib, as an anticancer. Blocking of HSP90 by the pretreatment of ganetespib exhibited significantly decreased accumulation of [18F]PTP-Ganetespib in MDA-MB-231 and MCF-7 cells, indicating the specific binding of [18F]PTP-Ganetespib to MDA-MB-231 and MCF-7 cells with high HSP90 expression. In the biodistribution and microPET imaging studies, the initial uptake into tumor was weaker than in other thoracic and abdominal organs, but [18F]PTP-Ganetespib was retained relatively longer in the tumor than other organs. The uptake of [18F]PTP-Ganetespib in tumors was not sufficient for further development as a tumor-specific PET imaging agent by itself, but this preliminary PET imaging study of [18F]PTP-Ganetespib can be basis for developing new PET imaging agents based on HSP90 inhibitor, ganetespib.
- Kang, Julie,Young Lee, Jun,Ta?, ?sa,More, Kunal N.,Kim, Hangun,Park, Jeong-Hoon,Chang, Dong-Jo
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p. 3658 - 3664
(2018/10/26)
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- 3. 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application (by machine translation)
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The invention discloses 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application. In particular, the invention relates to the formula (I) structure of 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivatives, its stereoisomers or its pharmaceutically acceptable salt, formula (I) in the definition of each substituent is as defined in the specification. These structure of novel compound with heat shock protein HSP90 inhibitory activity, can be used for treating cancer, neurodegenerative diseases, inflammatory diseases, autoimmune diseases, ischemic brain injury and the like, it has broad application prospects. (by machine translation)
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Paragraph 0295; 0309; 0310; 0311
(2017/07/01)
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- METHOD OF SYNTHESIZING SUBSTITUTED 2-ALKYL PHENOLS
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Methods of synthesizing 4-alkyl resorcinols and other substituted phenol compounds, according to formula (IV): or salts thereof, are disclosed, wherein the variables are defined herein.
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- TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY
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The present invention provides novel method of synthesis of compounds which inhibit the activity of Hsp90. In one embodiment, the present invention is a method of synthesis of a compound of formula (IA) cyclization of a compound of formula (II): in a base
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Page/Page column 36
(2009/07/17)
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- HYDRAZONAMIDE COMPOUNDS THAT MODULATE HSP90 ACTIVITY
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The present invention relates to substituted hydrazonamide compounds. The invention further relates to methods of inhibiting the activity of Hsρ90 in a subject in need thereof and methods for treating hyperproliferative disorders, such as cancer, in a sub
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Page/Page column 111
(2010/01/30)
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- TRIAZOLE COMPOUNDS THAT MODULATE HSP90 ACTIVITY
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The present invention relates to substituted triazole compounds and compositions comprising substituted triazole compounds. The invention further relates to methods of inhibiting the activity of Hsp90 in a subject in need thereof and methods for preventing or treating hyperproliferative disorders, such as cancer, in a subject in need thereof comprising administering to the subject a substituted triazole compound of the invention, or a composition comprising such a compound.
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Page/Page column 153; 196-197
(2008/12/08)
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