• GW501516 is a potent and selective peroxisome proliferator-activated receptor (PPAR) β/δ modulator.
• In vitro, GW501516 increased expression of the reverse cholesterol transporter ATP-binding cassette A1 and induced apolipoprotein A1-specific cholesterol efflux. In vivo, GW501516 dramatically increased serum high density lipoprotein cholesterol while lowering the levels of small-dense low density lipoprotein, fasting triglycerides, and fasting insulin when dosed to insulin-resistant middle-aged obese rhesus monkeys. Oliver, W.R. Jr., et al. "A selective peroxisome proliferator-activated receptor δ agonist promotes reverse cholesterol transport." Proc. Natl. Acad. Sci. USA 98: 5306-5311 (2001).
• Treatment of skeletal muscle cells by GW501516 resulted in the expression of genes involved in lipid utilization, β-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, the treatment also increased apolipoprotein-A1 specific efflux of intracellular cholesterol, indicating the muscle tissue is an important target of PPARβ/δ agonists. Dressel, U., et al. "The peroxisome proliferator-activated receptor β/δ agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells." Mol. Endocrinol. 17: 2477-2493 (2003).
• GW501516 induced fatty acid β-oxidation in L6 myotubes and in mouse skeletal muscles. GW501516 treatment to mice fed a high-fat diet ameliorated diet-induced obesity as well as insulin resistance. GW501516 treatment also dramatically improved diabetes, as demonstrated by the decrease in plasma glucose and blood insulin levels in genetically obese ob/ob mice. Tanaka, T., et al. "Activation of peroxisome proliferator-activated receptor δ induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome." Proc. Natl. Acad. Sci. USA 100: 15924-15929 (2003).
• GW501516 protected against cytotoxin-induced SH-SY5Y cell injury in vitro. It also significantly attenuated the ischemic brain damage and MPTP-induced depletion of striatal dopamine and related metabolite contents in mouse brain. Iwashita, A., et al. "Neuroprotective efficacy of the peroxisome proliferator-activated receptor δ-selective agonists in vitro and in vivo." J. Pharmacol. Exp. Ther. 320: 1087-1096 (2007).
• GW501516 treatment did not stimulate the growth of human cancer cell lines including HT29, HCT116, LS-174T, HepG2, and HuH7. Hollingshead, H.E., et al. "Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands do not potentiate growth of human cancer cell lines." Carcinogenesis 28: 2641-2649 (2007).
• GW501516 was identified as an orally active agent that would mimic or potentiate the effects of exercise. Narkar, V.A., et al. "AMPK and PPARδ agonists are exercise mimetics." Cell 134: 405-415 (2008).
• GW 501516 reduced the IFNγ-induced up-regulation of TNFα and inducible NO synthase, and showed anti-inflammatory activity. Defaux, A., et al. "Effects of the PPAR-β agonist GW501516 in an in vitro model of brain inflammation and antibody-induced demyelination." J. Neuroinflammation 6: 15 (2009).
• Another CAS number previously assigned to GW501516 free acid, namely 813458-54-7, has been deleted by CAS and is no longer in use.
• STRUCTURE ERROR ON WIKIPEDIA'S GW501516 PAGE: As of December 21, 2012, the structure shown on the Wikipedia page for GW501516 is not correct -- the version shown on Wikipedia is missing a methyl group on the benzene ring carrying sulfur- and oxygen-bearing substituents.
• Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
• This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
• Not available in some countries; not available to some institutions; not available for some uses.

M.W. 453.50
C21H18F3NO3S2
[317318-70-0]

Storage

Store at or below -20 ºC

Solubility

Soluble in DMSO

Disposal

A LC Labs的关于纯度的更多信息我们知道许多情况下，由于不合格试剂的虚假结果，导致无法识别的纯度问题导致大量研究工作受到损害，甚至变得毫无用处。以下是信号转导试剂业务中产品纯度或活性问题的一些示例：几年前，一家主要的供应商向许多实验室提供了错误的激酶抑制剂H7异构体。错误的异构体具有明显不同的生物学特性，并且由此获得的结果也不正确。我们上级组织的科学家检测到了这个问题，并与一个合作的学术实验室一起发布了更正的数据[ Biochem。生物物理学。Res。通讯 187：657-663（1993）]。冈田酸产品存在很大的稳定性问题。冈田酸虽然散装形式相当稳定，但细分为亚毫克量并真空干燥以最终销售后，其降解率可立即高达40％或更高。许多供应商没有对包装后的最终产品进行适当的测试，我们的分析表明，其他一些供应商的冈田酸在某些情况下的纯度不足60％。客户一再告诉我们，冈田酸比其他供应商的原料更具活性。白屈菜红碱氯化物由于一些人们不了解的问题而引起了极大的动荡。首先，多年来，我们注意到白屈菜红碱的其他一些来源也被大量的生物活性杂质污染，例如血红碱，很难从天然来源的白屈菜红碱中去除。相比之下，我们的白屈菜红碱是通过严格的多步方法制备的，其中包括HPLC和结晶步骤，并且所得纯度极高且可重现。第二，研究人员告知我们，其他供应商的白屈菜红碱在不同批次之间显示出不同的生物活性。第三，在一些出版物中建议白屈菜红碱没有显示出最初归因于1991年的有效的PKC抑制活性[ Biochem.Chem.Soc。，1993，5，2，3]。生物物理学。Res。通讯 172：993-999（1991）]。1991年的这份报告使用了从天然来源分离的白屈菜红碱，它可能已经被抑制PKC催化活性的干扰化合物所污染。但是，可能不会排除其他更复杂的解释。但却是很清楚，白屈菜红有力块多效应的PKC活化剂，如佛波醇酯，但有可能的是，这些影响从PKC的相互作用，不涉及实际的激酶活性的抑制导致本身。据报道，1994年Rottlerin是PKCδ的选择性抑制剂，但最近的研究未能显示出在相似浓度下任何PKC抑制活性。1994年的研究使用了来自植物来源的rottlerin，当我们分析多个批次时，该物质一直被证明含有大量杂质。随后，非常有能力的实验室未能复制原始的rottlerin结果，以及其他考虑因素，迫使我们停止生产该产品。单击此处，可以在我们的rotterlin产品页面上找到更多信息。来自三个不同的非附属学术实验室的研究人员告知我们，我们的PMA在各种生物系统中的性能要优于从其他来源获得的材料。