CAS |
122320-73-4 |
Chinese Name |
罗格列酮 |
English Name |
Rosiglitazone |
Synonyms |
罗格列酮;罗格列酮碱;BRL 49653 |
Molecular Formula |
C18H19N3O3S |
Molecular Weight |
357.43 |
Solubility |
Soluble in DMSO ≥10mg/mL |
Purity |
HPLC≥98% |
Appearance |
White to off-white Solid |
Storage |
Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
EC |
EINECS 924-121-1 |
MDL |
MFCD00871760 |
SMILES |
O=C(N1)SC(CC2=CC=C(OCCN(C)C3=NC=CC=C3)C=C2)C1=O |
InChIKey |
YASAKCUCGLMORW-UHFFFAOYSA-N |
InChI |
InChI=1S/C18H19N3O3S/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15/h2-9,15H,10-12H2,1H3,(H,20,22,23) |
PubChem CID |
77999 |
Target Point |
PPAR;TRP Channe |
Passage |
Cell Cycle;DNA Damage/DNA Repair;Metabolic Enzyme&Protease;Membrane Transporter/Ion Channel |
Background |
Rosiglitazone is an effective PPAR γ Selective agonists. Rosiglitazone is a TRPC5 activator and TRPM3 inhibitor. Rosiglitazone can be used for research on obesity, diabetes, aging and ovarian cancer. |
Biological Activity |
Rosiglitazone (BRL49653) 是一种有效的噻唑烷二酮胰岛素增敏剂。 Rosiglitazone是一种选择性的PPARγ 激动剂,对 PPARγ1,PPARγ2 和 PPARγ 的EC50 分别为 30 nM,100 nM 和 60 nM。[1-5] |
IC50 |
PPARγ1:30nM(EC50);PPARγ2:100nM(EC50)[1-5] |
In Vitro |
罗格列酮是PPARγ的有效选择性激活剂,PPARγ1和PPARγ2的EC50分别为30 nM和100 nM,PPARγ的Kd为40 nM。罗格列酮(BRL49653,0.1,1,10μM)促进C3H10T1/2干细胞分化为脂肪细胞[1]。罗格列酮(化合物6)激活PPARγ,EC50为60 nM [2]。罗格列酮(1μM)激活PPARγ,其结合NF-α1启动子以激活神经元中的基因转录。罗格列酮(1μM)还可以保护Neuro2A细胞和海马神经元免受氧化应激,并以NF-α1依赖性方式上调BCL-2的表达[3]。罗格列酮完全抑制TRPM3,对硝苯地平和PregS诱发活性的IC50值为9.5和4.6μM,但这种效应不是通过PPARγ。罗格列酮在较高浓度下抑制TRPM2,IC50为22.5μM。罗格列酮是TRPC5通道的强刺激剂,EC50为 30μM[4]。 |
In Vivo |
罗格列酮(5mg/kg,口服)降低糖尿病大鼠的血清葡萄糖。罗格列酮还可降低糖尿病组的IL-6,TNF-α和VCAM-1水平。与糖尿病组和Los治疗组相比,罗格列酮联合氯沙坦增加葡萄糖。罗格列酮显著改善内皮功能障碍,表现为对PE和Ang II的收缩反应显著降低,并且从糖尿病大鼠分离的主动脉中ACh引起的松弛增强[5]。 |
Cell Experiment |
C3H10T1/2细胞在补充有10%胎牛血清的DME培养基中的24孔板中生长。每3天更换培养基和化合物(罗格列酮)。细胞在第7天用油红O染色并拍照[1]。 |
Animal Experiment |
大鼠静脉注射38mg/kg链脲佐菌素,48小时后,通过尿糖尿症鉴定糖尿病,然后测量随机血糖,这一天被视为第0天。血清葡萄糖水平为220-300mg/dL的动物被选择用于本研究。将大鼠随机分成5组,每日给药8周:第1组:仅给予载体的对照非糖尿病大鼠(0.5mL/kg口服0.5%羧甲基纤维素),第2组:给予载体的对照糖尿病大鼠,组3:接受罗格列酮(5mg/kg口服)的糖尿病大鼠,第4组:接受氯沙坦(2mg/kg,口服)的糖尿病大鼠,和第5组:接受罗格列酮和氯沙坦的糖尿病大鼠[2]。 |
Kinase Experiment |
编码PPARγ1的氨基酸174-475的cDNA通过聚合酶链反应扩增,并插入细菌表达载体pGEX-2T中。 GST-PPARγLBD在BL21(DE3)plysS细胞和提取物中表达。对于饱和结合分析,将细菌提取物(100μg蛋白质)在含有10mM Tris(pH 8.0),50mM KCl,10mM二硫苏糖醇和[3H] -BRL49653的缓冲液中于4℃温育3小时(比活性,在存在或不存在未标记的罗格列酮的情况下,40Ci/mmol)。通过1-mL Sephadex G-25脱盐柱洗脱,将结合与游离放射性分离。结合的放射性在柱空隙体积中洗脱,并通过液体闪烁计数[1]进行定量。 |
Data Literature Source |
[1]. Lehmann JM,et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953-6. [2]. Willson TM,et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8. [3]. Thouennon E,et al. Rosiglitazone-activated PPARγ induces neurotrophic factor-α1 transcription contributing to neuroprotection. J Neurochem. 2015 Aug;134(3):463-70. [4]. Majeed Y,et al. Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol Pharmacol. 2011 Jun;79(6):1023-30. [5]. Ateyya H,et al. Beneficial effects of rosiglitazone and losartan combination in diabetic rats. Can J Physiol Pharmacol. 2018 Mar;96(3):215-220 |
Unit |
Bottle |
Specification |
50mg 10mM*1mL in DMSO 100mg |