Discovery of Pyrazole-Based Positron Emission Tomography Agent that Maps Histone Deacetylase 6 (HDAC6) in the Nonhuman Primate Brain
Year: 2025
Type: article
Abstract: Histone deacetylase 6 (HDAC6) is a crucial target for the development of pharmaceuticals used in the treatment of neurodegenerative disorders. Here, we identified 16a as a candidate of positron emission tomography (PET) tracer for HDAC6 imaging from pyrazole derivatives, which showed strong HDAC6 affinity (Kd = 1.66 nM) and higher accumulation in the brain of wild-type mice than in HDAC6 knockout mice. Following radiolabeling with fluorine-18, PET with [18F]16a exhibited heterogeneous uptake of radioactivity, corresponding to the biological distribution of HDAC6 in the monkey brain. These radioactive distributions were homogeneously diminished by the preadministration of ACY-775, a potent inhibitor of HDAC6, suggesting that radioactive accumulation in PET images could reflect the specific binding of [18F]16a with HDAC6. Thus, [18F]16a is a promising PET tracer for HDAC6 imaging that motivates future clinical research.
Source: Journal of Medicinal Chemistry
Authors: Tomoteru Yamasaki, Norio Ohyabu, Takeshi Wakabayashi, Ignacio Ibáñez, Kouichi Iwanaga, Satoshi Yamamoto, Masahiko Hattori, Taku Sugita, Michiko Terada, Tomohiro Onishi, Sho Sato, Yohei Kosugi, Akihiro Takano, Paul McQuade, Takamitsu Maru, Naomi Inui, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Chie Seki, Shoko Uchida, Takafumi Minamimoto, Makoto Higuchi, Makoto Fushimi, Ming-Rong Zhang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: Development of PET probes for cyclic nucleotide phosphodiesterases 7, In vivo制御に向けた人工リガンド・受容体ペア設計の学理構築, G2963015916, G3153944560, G3374338189, Development of Radio-Senolytics for Imaging and Deleting Senescent Cells, G3691837540, G3786735645, G4737930782, G6167594335, G6646357127, PET study for AMPA-TARPg8 complex in epilepsy., G7619541072
OpenAlex ID: W4415385083