In 2022,Koike, Tatsuki; Constantinescu, Cristian C.; Ikeda, Shuhei; Nishi, Toshiya; Sunahara, Eiji; Miyamoto, Maki; Cole, Patricia; Barret, Olivier; Alagille, David; Papin, Caroline; Morley, Thomas; Fowles, Krista; Seibyl, John; Tamagnan, Gilles; Kuroita, Takanobu published an article in European Journal of Nuclear Medicine and Molecular Imaging. The title of the article was 《Preclinical characterization of [18F]T-008, a novel PET imaging radioligand for cholesterol 24-hydroxylase》.Recommanded Product: 18621-18-6 The author mentioned the following in the article:
Cholesterol 24-hydroxylase (CH24H) is a brain-specific enzyme that plays a major role in brain cholesterol homeostasis by converting cholesterol into 24S-hydroxycholesterol. The selective CH24H inhibitor soticlestat (TAK-935) is being pursued as a drug for treatment of seizures in developmental and epileptic encephalopathies. Herein, we describe the successful discovery and the preclin. validation of the novel radiolabeled CH24H ligand (3-[18F]fluoroazetidin-1-yl){1-[4-(4-fluorophenyl)pyrimidin-5-yl]piperidin-4-yl}methanone ([18F]T-008) and its tritiated analog, [3H]T-008. In vitro autoradiog. (ARG) studies in the CH24H wild-type (WT) and knockout (KO) mouse brain sections were conducted using [3H]T-008. PET imaging was conducted in two adult rhesus macaques using [18F]T-008. Each macaque received two test-retest baseline scans and a series of two blocking doses of soticlestat administered prior to [18F]T-008 to determine the CH24H enzyme occupancy. PET data were analyzed with Logan graphical anal. using plasma input. A Lassen plot was applied to estimate CH24H enzyme occupancy by soticlestat. In ARG studies, binding of [3H]T-008 was specific to CH24H in the mouse brain sections, which was not observed in CH24H KO or in wild-type mice after pretreatment with soticlestat. In rhesus PET studies, the rank order of [18F]T-008 uptake was striatum > cortical regions > cerebellum, which was consistent with CH24H distribution in the brain. Pre-blocking with soticlestat reduced the maximum uptake and increased the washout in all brain regions in a dose-dependent manner. Calculated global occupancy values for soticlestat at a dose of 0.89 mg/kg were 97-98%, indicating maximum occupancy. The preclin. in vitro and in vivo evaluation of labeled T-008 demonstrates that [18F]T-008 is suitable for imaging CH24H in the brain and warrants further studies in humans. In the experimental materials used by the author, we found Azetidin-3-ol hydrochloride(cas: 18621-18-6Recommanded Product: 18621-18-6)
Azetidin-3-ol hydrochloride(cas:18621-18-6) is one of azetidine.Azetidines (azacyclobutanes) constitute a well-known class of heterocyclic compounds. Azetidine scaffold has been discovered in several natural products.Recommanded Product: 18621-18-6 Several pharmacologically important synthetic compounds also contain azetidine ring. Because of inherent ring strain, the synthesis of azetidines is a challenging endeavor.
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