化合物GSK256066 T6054

Product Introduction
Bioactivity


英文名: GSK256066

描述: GSK256066 是高亲和力的、选择性的PDE4抑制剂，IC50=3.2 pM，被开发用于慢性阻塞性肺病的研究。

体外活性: GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 x 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 x 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity. [1]

体内活性: GSK256066 inhibits the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 ml/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the male CD rat. [1] GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats. [2] GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes. [3]

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: DMSO : 10 mg/mL (19.28 mM)


关键字: Phosphodiesterase (PDE) | PDE | obstructive | disease | chronic | high-affinity | inhibit | phosphodiesterase | PDE4B | Inhibitor | GSK 256066 | pulmonary | GSK256066 | GSK-256066

相关产品: Bucladesine sodium | Avanafil | Autotaxin modulator 1 | Tofimilast | PDE9-IN-(S)-C33 | Bay 60-7550 | ONO-8430506 | PDE4B-IN-2 | Oglemilast | Autotaxin-IN-3

相关库: Drug Repurposing Compound Library | Anti-Neurodegenerative Disease Compound Library | ReFRAME Related Library | Anti-Metabolism Disease Compound Library | Bioactive Compounds Library Max | Inhibitor Library | Metabolism Compound Library | NO PAINS Compound Library | Anti-Alzheimer's Disease Compound Library | Bioactive Compound Library

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注：该产品未在中华人民共和国食品药品监督管理部门申请医疗器械注册和备案，不可用于临床诊断或治疗等相关用途