S-(+)-Rolipram

• 产品号: S2127
• CAS号: 85416-73-5
• 分子式: C16H21NO3
• 分子量: 275.34284
• 保 存: -20°C

产品别名

• 标题: S-(+)-Rolipram
• IUPAC标准名: (4S)-4-[3-(cyclopentyloxy)-4-methoxyphenyl]pyrrolidin-2-one
• IUPAC传统名: (+)-rolipram

产品登记号

• CAS号: 85416-73-5

产品性质

• 成盐信息: Free Base
• 保存条件: -20°C

产品详细信息

详细说明 (English)

Research Area

• Description: Neurological Disease

Biological Activity

• Description: S-(+)-Rolipram inhibits human monocyte cyclic AMP-specific PDE4 with IC50 of 0.75 μM.
• Targets: PDE4
• IC50: 750 nM ^[1]
• In Vitro: S-(+)-Rolipram suppresses LPS-induced TNFα expression from human monocyte through inhibiting PDE4 with IC50 about 2 μM. ^[1] 1 μM S-(+)-Rolipram significantly antagonizes ovalbumin (OA) induced concentration-related contractions of tracheal rings which are isolated from OA-sensitized guinea pigs. ^[2] S-(+)-Rolipram inhibits PDE4 activity in a CHO-K1 cell line which stably expresses a recombinant full length human PDE-4a with IC50 at 450 nM. ^[3] Treatment of the human glioma cell line A-172 with Rolipram (including both R- and S-enantiomers of Rolipram) results in increased expression of the cell cycle inhibitors p21 ^[Cip1] and p27 ^[Kip1], and decreased activity of cdk2, a cyclindependent kinase essential for cell cycle progression. As a result, the proliferation of A-172 cells is inhibited, with induction of a G1 block. Eventually, Rolipram-treated A-172 cells undergo differentiation, which is followed by apoptotic cell death. ^[4]
• In Vivo: In anesthetized, ventilated OA-sensitive guinea pigs, S-(+)-Rolipram reduces OA-induced bronchoconstriction with ID50 values of approximately 0.25 mg/kg i.v. Histamine- and leukotriene D4-induced bronchoconstriction are not affected by doses of S-(+)-Rolipram which abolishes the response to OA. Higher doses (3-10 mg/kg) reduce histamine-, but not the leukotriene D4-induced bronchoconstriction. In conscious OA-sensitive guinea pigs, intragastric pretreatment with S-(+)-Rolipram dose-dependently reduces both the OA-induced decreases in specific conductance as well as the corresponding pulmonary eosinophil influx as assessed by both bronchoalveolar lavage and histological evaluation. ^[2]
• Clinical Trials: Rolipram (including both R- and S-enantiomers of Rolipram) is under the Phase I clinical trial for its antidepressant effects on cAMP specific phosphodiesterase (PDE4) in depressed patients.

Protocol

• Protocol: Kinase Assay ^[1]
• PDE Assay: PDE activity is determined by the two-step radioisotope method of Thompson et al (1979). The reaction mixture contains: Tris-HCl 20 mM (pH 8.0), MgCl₂ 10 mM, 2-mercaptoethanol 4 mM, ethyleneglycol-bis-(f-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) 0.2 mM, bovine serum albumin, 0.05 mg/mL. Unless otherwise stated, the substrate concentration is 1 μM. The IC50 values (concentration which produced 50% inhibition of substrate hydrolysis) for the compounds are determined from concentration (0.1 nM to 40 μM)-response curves. At least three concentration-response curves are generated for each agent.
• Protocol: Animal Study ^[2]
• Animal Models: Male Hartley guinea pigs
• Formulation: S-(+)-Rolipram is dissolved in 100% PEG at an appropriate concentration.
• Doses: 1 mL/kg
• Administration: Administered via i.v.

References

• References: [1] Souness JE, et al. Br J Pharmacol, 1996, 118(3), 649-658
• References: [2] Underwood DC, et al. J Pharmacol Exp Ther, 1993, 266(1), 306-313
• References: [3] Pon DJ, et al. Cell Biochem Biophys, 1998, 29(1-2), 159-178.
• References: [4] Chen TC, et al. Cancer Biol Ther, 2002, 1(3), 268-276.

参考文献

• Souness JE, et al. Br J Pharmacol, 1996, 118(3), 649-658
• Underwood DC, et al. J Pharmacol Exp Ther, 1993, 266(1), 306-313
• Pon DJ, et al. Cell Biochem Biophys, 1998, 29(1-2), 159-178.
• Chen TC, et al. Cancer Biol Ther, 2002, 1(3), 268-276.