PPARγ (Kd = 40 nM); PPARγ (EC50 = 60 nM); TRPC5 (EC50 = 30 μM); TRPM3

脂肪细胞分化是多能 C3H10T1/2 干细胞用盐酸罗格列酮 (0.1–10 μM) 处理 72 小时的结果[1]。除了保护 Neuro2A 细胞和海马神经元免受氧化应激外，Rosiglitazone Hydrochronide（1 μM，24 小时）还可激活 PPARγ，后者与 NF-κ1 启动子结合以激活基因转录[3]。它还上调 BCL-2 表达。盐酸罗格列酮（0.01-100 盐酸罗格列酮（0.5-50 μM，7 天））可抑制卵巢癌细胞的增殖[7]。在 A2780 和 SKOV3 细胞中，连续 7 天给予 5 μM 可抑制细胞衰老的变化由奥拉帕尼引起并促进细胞凋亡[7]。

在糖尿病大鼠中，盐酸罗格列酮（口服治疗，5 mg/kg，每天，持续 8 周）可降低血糖水平[5]。盐酸罗格列酮（腹腔注射，3 mg/kg/天）通过抑制雄性 Wistar 大鼠 M1 巨噬细胞极化并激活 PPARγ 和 RXRα，减轻香烟烟雾引起的气道炎症[6]。盐酸罗格列酮（腹膜内注射，10 mg/kg，每两天一次）可抑制 A2780 和 SKOV3 小鼠皮下异种移植模型中的皮下卵巢癌生长[7]。

在这里，我们报告噻唑烷二酮类是过氧化物酶体增殖物激活受体γ（PPAR-γ）的强效和选择性激活剂，PPAR-γ是核受体超家族的成员，最近被证明在脂肪生成中起作用。这些药物中最有效的是BRL49653，它以约40nM的Kd与PPARγ结合。用BRL49653处理多能性C3H10T1/2干细胞可有效分化为脂肪细胞。这些数据首次证明了高亲和力PPAR配体，并提供了强有力的证据，表明PPAR-γ是噻唑烷二酮类脂肪生成作用的分子靶点。此外，这些数据提出了一种有趣的可能性，即PPAR-γ是这类化合物治疗作用的靶点。[1]

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通过聚合酶链式反应扩增编码PPARγ1氨基酸174-475的cDNA，并将其插入细菌表达载体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，在存在或不存在未标记的罗格列酮的情况下，将细菌提取物（100μg蛋白质）在4°C下在含有10 mM Tris（pH 8.0）、50 mM KCl、10 mM二硫苏糖醇和[3H]-BRL49653（比活度，40 Ci/mmol）的缓冲液中孵育3小时。通过1-mL Sephadex G-25脱盐柱洗脱，将结合放射性与游离放射性分离。结合放射性在柱空隙体积中洗脱，并通过液体闪烁计数进行定量[1]。

细胞增殖测定[7]
细胞类型： A2780 和 SKOV3 细胞
测试浓度： 0.5-50 μM
孵育时间： 1- 7 天
实验结果： 以时间依赖性和浓度依赖性的方式抑制细胞增殖。

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蛋白质印迹分析[3]
细胞类型： 海马神经元
测试浓度： 1 μM
孵育时间：1 μM
实验结果：增加 NF-α1 和 BCL-2 蛋白水平。

Animal/Disease Models: Streptozotocin (STZ)-induced diabetic rats[5]
Doses: 5 mg/kg
Route of Administration: Oral administration, daily for 8 weeks.
Experimental Results: diminished IL-6, TNF-α, and VCAM-1 levels in diabetic group. Displayed lower levels of lipid peroxidation and NOx with an increase in aortic GSH and SOD levels compared to diabetic groups.

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Animal/Disease Models: Male Wistar rats[6]
Doses: 3 mg/kg/day
Route of Administration: intraperitoneal (ip)injection, twice a day, 6 days per week for 12 weeks
Experimental Results: Ameliorated emphysema, elevated PEF, and higher level of total cells, neutrophils and cytokines (TNF-α and IL-1β) induced by cigarette smoke (CS). Inhibited CS-induced M1 macrophage polarization and diminished the ratio of M1/M2.

[1]. 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]. 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]. Rosiglitazone-activated PPARγ induces neurotrophic factor-α1 transcription contributing to neuroprotection. J Neurochem. 2015 Aug;134(3):463-70.

[4]. Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol Pharmacol. 2011 Jun;79(6):1023-30.

[5]. Beneficial effects of rosiglitazone and losartan combination in diabetic rats. Can J Physiol Pharmacol. 2018 Mar;96(3):215-220.

[6]. Rosiglitazone ameliorated airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα. Int Immunopharmacol. 2021 Aug;97:107809.

[7]. Rosiglitazone ameliorates senescence and promotes apoptosis in ovarian cancer induced by olaparib. Cancer Chemother Pharmacol. 2020 Feb;85(2):273-284.

Background: Rosiglitazone, an exogenous ligand of PPARγ, plays an important anti-inflammatory role during the inflammation caused by cigarette smoke (CS). CS exposure induces pulmonary inflammation via activating macrophage polarization. However, the effects of rosiglitazone on macrophage polarization induced by CS are unclear.[6]
Methods: 36 male Wistar rats were randomly divided into 3 groups: control, CS and ROSI. In the CS group, rats were passively exposed to cigarette smoke for consecutive 3 months. In the ROSI group, rats were treated with rosiglitazone (3 mg/kg/day, ip) during CS exposure period. Alveolar macrophages of rats were isolated and cultured with CSE. The slices of lung tissues were stained with hematoxylin and eosin. The histomorphology was observed to evaluate emphysema and the pulmonary function was detected. Cells in bronchoalveolar lavage fluid (BALF) were examined and the expression of cytokines TNF-α and IL-1β was detected by ELISA and qPCR. The alveolar macrophage polarization was evaluated by immunohistochemistry and flow cytometry assay in vivo and by qPCR in vitro. The protein level of PPARγ and RXRα was measured by Western blot.[6]
Results: CS exposure induced significant emphysema, diminished FEV0.2/FVC, elevated PEF, and higher level of total cells, neutrophils and cytokines (TNF-α and IL-1β) in BALF compared with control group, whereas rosiglitazone partly ameliorated above disorders. CS exposure activated M1 and M2 macrophage polarization in vivo and in vitro, whereas rosiglitazone inhibited CS induced M1 macrophage polarization and decreased the ratio of M1/M2. The effects of rosiglitazone on macrophage polarization were partly blocked after AMs treated with the antagonists of PPARγ and RXRα, and were synergistically enhanced by the agonist of RXRα. CS exposure decreased the expression of PPARγ and RXRα in lung tissues and AMs, and rosiglitazone partly reversed CS-mediated suppression of PPARγ and RXRα.[6]
Conclusion: Rosiglitazone ameliorated the emphysema and inflammation in lung tissues induced by CS exposure via inhibiting the M1 macrophage polarization through activating PPARγ and RXRα.[6]

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Objective: Senescence mechanisms are vital to resistance to long-term olaparib maintenance treatment. Recently, peroxisome proliferator-activated receptor-γ agonists (e.g., rosiglitazone) have been reported to ameliorate the senescence-like phenotype by modulating inflammatory mediator production. This study examined synergistic effects on the anti-tumor activity of rosiglitazone combined with olaparib in ovarian cancer treatment.[7]
Methods: A2780 and SKOV3 mouse subcutaneous xenograft models were established for observing anti-tumor effects in living organisms and were randomly split into combination (both olaparib and rosiglitazone), rosiglitazone (10 mg/kg), olaparib (10 mg/kg), control (solvent) groups that received treatment once every 2 or 3 days (n = 6 per group). Cell counting kit-8 (CCK-8) assays were used to test the influences of rosiglitazone and olaparib on cell proliferation. PI and Annexin-V-FITC staining was used with flow cytometry to assess the cell cycle distribution and cell apoptosis. Senescence-associated β-galactosidase (SA-β-Gal) staining was used to observe cellular senescence. We performed quantitative real-time polymerase chain reaction assays to study the senescence-related secretory phenotype (SASP). [7]
Results: Olaparib and rosiglitazone were observed to synergistically retard subcutaneous ovarian cancer growth in vivo, and synergistically suppress ovarian cancer cell proliferation in vitro. Compared with olaparib alone, the percentage of positive cells expressed SA-β-gal and SASP were significantly decreased in the treatment of combination of olaparib and rosiglitazone. Furthermore, olaparib plus rosiglitazone increased the percentage of apoptosis in ovarian cancer cell compared with olaparib alone. In A2780 cells, it showed lower expression of P53, phospho-p53 (Ser15), P21, and P18 protein in combination treatment compared with olaparib alone. While, in SKOV3 cells, it showed lower expression of phosphor-retinoblastoma protein (Rb) (Ser807/811), and higher expression of cyclin D1, P21, and P16 protein in combination treatment compared with olaparib alone.[7]
Conclusions: Rosiglitazone combined with olaparib can help manage ovarian cancer by ameliorating olaparib-induced senescence and improving anti-tumor effects.

C18H19N3O3S.HCL

393.89

393.091

302543-62-0

Rosiglitazone maleate;155141-29-0;Rosiglitazone;122320-73-4;Rosiglitazone potassium;316371-84-3;Rosiglitazone-d3;1132641-22-5

9865387

Typically exists as White to off-white solids at room temperature

3.621

96.83

2

6

7

26

469

0

CN(C1=CC=CC=N1)CCOC2=CC=C(CC3C(NC(S3)=O)=O)C=C2.Cl

XRSCTTPDKURIIJ-UHFFFAOYSA-N

InChI=1S/C18H19N3O3S.ClH/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);1H

5-(4-(2-(methyl(pyridin-2-yl)amino)ethoxy)benzyl)thiazolidine-2,4-dione hydrochloride

Rosiglitazone HCl; Rosiglitazone Hydrochloride; HSDB-7555; BRL-49653 HCl; BRL49653; TDZ-01; BRL 49653; HSDB 7555; HSDB7555; TDZ 01; TDZ01; Rosiglitazone. trade name Avandia; 302543-62-0; ROSIGLITAZONE HCl; Rosiglitazone (hydrochloride); BRL 49653 (hydrochloride); 5-[[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione;hydrochloride; Rosiglitazone hydrochloride [WHO-DD]; S3055SS582;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
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