Lixazinone  (Synonyms: RS-82856)

Lixazinone (RS-82856) hydrogensulfate is a selective inhibitor of cGMP-inhibited phosphodiesterase (PDE3) with an IC₅₀ value of 22 nM. Lixazinone hydrogensulfate exhibits positive inotropic effects, afterload reduction and antithrombotic properties. Lixazinone hydrogensulfate increases cyclic adenosine monophosphate (cAMP) levels in human platelets, inhibits thrombin-induced aggregation of human platelets, and blocks the photolabeling of PDE3 active sites by [³²P]cGMP. Lixazinone hydrogensulfate can be used in the research of polycystic kidney disease and congestive heart failure^[1][2][3][4].

Lixazinone (3Lixazinone hydrogensulfate (0.5-1 μM; 5 min at 30 °C) 可强效且选择性地抑制人血小板 PDE3，0.5 μM 浓度下对 PDE3 活性的抑制率达 97%，而 1 μM 浓度下对 PDE2 活性仅产生极微弱的影响^[1]。
Lixazinone hydrogensulfate (1 μM; 1 min at 37 °C) 可使人血小板中[³H]cAMP 水平升高 177%^[1]。
Lixazinone hydrogensulfate (1 μM; 1 min at 37 °C pre-incubation) 可完全抑制凝血酶诱导的人血小板聚集^[1]。
Lixazinone hydrogensulfate (1 μM; 1 min at 37 °C) 可适度提升经 20 nM PGI₂ 处理的人血小板中[³H]cAMP 的水平^[1]。
Lixazinone hydrogensulfate (300 nM; 15 min dark at 0°C, 15 min UV irradiation) 可抑制大鼠血小板裂解液和大鼠心脏匀浆中 115 kDa PDE III 亚基的光标记^[2]。
Lixazinone hydrogensulfate (10 μM; 60 min) 可使静息状态下的 MDCK 细胞内 cAMP 水平升高 22%^[3]。
Lixazinone hydrogensulfate (10 μM) 在转染的静止 MDCK 细胞中可使 PKA 激活 27%^[3]。
Lixazinone hydrogensulfate (10 μM; 72 hrs) 可显著促进静止 MDCK 细胞的有丝分裂，该作用通过 [³H]-胸苷掺入实验检测^[3]。
Lixazinone hydrogensulfate (10 μM; 5 mins) 可在静息 MDCK 细胞中显著激活 B-Raf 激酶活性，但对 Raf-1 激酶活性无影响^[3]。
Lixazinone hydrogensulfate (10 μM; 1 hr) 可使静息状态下的 MDCK 细胞中 ERK 激酶活性提升 810%^[3]。
Lixazinone hydrogensulfate (10 μM; 4 hrs) 可使静止状态的 MDCK 细胞中 cyclin D 激酶活性提升 83%，cyclin E 激酶活性提升 58%^[3]。
Lixazinone hydrogensulfate (10 μM; 8 hrs) 对静息状态下的 MDCK 细胞中 p21 或 p27 的表达无显著影响^[3]。
Lixazinone hydrogensulfate (10 μM; 24 hrs) 可强效抑制大鼠肾小球系膜细胞的有丝分裂，该作用通过[³H]-胸苷掺入实验检测^[3]。
Lixazinone hydrogensulfate (1 nM-10 μM) 可抑制原代培养大鼠系膜细胞总匀浆中的 cAMP 磷酸二酯酶活性，其 IC₅₀ 为 2.85 nM，该效力与其对有丝分裂的抑制作用相关^[4]。 μM) 可特异性抑制 PDE3 亚型，该亚型在 MDCK 细胞提取物中占总 cAMP-PDE 活性的 15%^[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

384.48

C₂₁H₂₈N₄O₃

94192-59-3

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Cheng J, et al. Lixazinone stimulates mitogenesis of Madin-Darby canine kidney cells. Exp Biol Med (Maywood). 2006;231(3):288-295.  [Content Brief]

  [2]. Tang KM, et al. Photoaffinity labelling of cyclic GMP-inhibited phosphodiesterase (PDE III) in human and rat platelets and rat tissues: effects of phosphodiesterase inhibitors. Eur J Pharmacol. 1994;268(1):105-114.  [Content Brief]

  [3]. Chini CC, et al. Compartmentalization of cAMP signaling in mesangial cells by phosphodiesterase isozymes PDE3 and PDE4. Regulation of superoxidation and mitogenesis. J Biol Chem. 1997 Apr 11;272(15):9854-9.  [Content Brief]