N-[1-[4-[2-クロロ-4-(トリフルオロメトキシ)フェノキシ]-3-クロロピリジン-2-イル]ピペリジン-4-イル]-N′-(3-ピリジル)チオ尿素 化学特性,用途語,生産方法
説明
DO264 is an inhibitor of α/β-hydrolase domain-containing protein 12 (ABHD12; IC
50 = 11 nM). It inhibits ABHD12-dependent hydrolysis of lysophosphatidylserine (lyso-PS) in mouse brain membrane lysates (IC
50 = 2.8 nM) and human THP-1 cells. DO264 increases levels of chemokine (C-C motif) ligand 3 (CCL3), CCL4, TNF-α, and IL-1β in M1-polarized THP-1 macrophages. It potentiates ferroptotic cell death induced by the glutathione peroxidase 4 (GPX4) inhibitor RSL3 in HT1080 fibrosarcoma and SU-DHL-5 B cell lymphoma cells when used at a concentration of 1 μM.
In vivo, DO264 (30 mg/kg per day for four weeks) increases levels of 1-stearoyl-2-hydroxy-
sn-glycero-3-PS, 1-arachidonoyl-2-hydroxy-
sn-glycero-3-PS, 1-docosanoyl-2-hydroxy-
sn-glycero-3-PS, 1-stearoyl-2-arachidonoyl-
sn-glycero-3-PS, and 1-oleoyl-2-arachidonoyl-
sn-glycero-3-PS in mouse brain. It increases levels of CCL2, CCL3, and CCL5 in bronchoalveolar lavage fluid (BALF) and decreases survival in a mouse model of infection with lymphocytic choriomeningitis virus (LCMV) clone 13 when administered at a dose of 30 mg/kg.
使用
DO264 is a potent inhibitor of ABHD12 (α/β-hydrolase domain-containing 12) which shows negligible interaction with other serine hydrolases as determined by activity-based protein profiling.
N-[1-[4-[2-クロロ-4-(トリフルオロメトキシ)フェノキシ]-3-クロロピリジン-2-イル]ピペリジン-4-イル]-N′-(3-ピリジル)チオ尿素 上流と下流の製品情報
原材料
準備製品