GSK 0660 is a potent PPARβ antagonist with an IC50 value of 155nM [1]. GSK 0660 can prevent pathological angiogenesis and tubular structure formation by inhibiting the activity of PPARβ [2]. GSK 0660 has been widely used to regulate the activation of P38 MAPK and stimulate the migration of corneal epithelial cells[3].
In vitro, GSK 0660 treatment (5µM) for 24 hours led to a decrease in the viability of cholesteatoma Keratinocytes, inhibition of PDK1 expression, and a reduction in the phosphorylation levels of AKT and GSK3β[4]. 0.2µM of GSK 0660 treatment for 24 hours significantly inhibited 6-hydroxydopamine (6-OHDA)-induced cell death in SH-SY5Y cells, prevented oxidative stress, and increased the activity of SOD protein[5]. Treatment with 10µM GSK 0660 for 24 hours significantly reduced the expression of CCL8 and CXCL10 in human retinal microvascular endothelial cells (HRMECs) induced by TNF-α, and decreased cell adhesion[6].
In vivo, GSK 0660 treatment via daily intraperitoneal injection at a dose of 20mg/kg for 21 days significantly inhibited tumor growth and reduced tumor weight in the CT-26 xenograft mouse model[7]. Daily intraperitoneal injection of a 1mg/kg dose of GSK 0660 for 7 days can eliminate the effects of central injection of leptin on the body weight and food intake of rats, and significantly increase the serum insulin level[8].
References:
[1] Shearer B G, Steger D J, Way J M, et al. Identification and characterization of a selective peroxisome proliferator-activated receptor β/δ (NR1C2) antagonist[J]. Molecular endocrinology, 2008, 22(2): 523-529.
[2] Savage S R, Capozzi M E, McCollum G W, et al. The effects of pharmacologic manipulation of Peroxisome Proliferator-Activated Receptor β/on pathological angiogenesis[J]. Investigative Ophthalmology & Visual Science, 2012, 53(14): 2997-2997.
[3] Zhang Z, Pan Z, Zhang F, et al. Pparß Antagonist Mediates Increases in Human Corneal Epithelial Cell Migration Through P38 Mapk Activation[J]. Investigative Ophthalmology & Visual Science, 2010, 51(13): 1973-1973.
[4] Zhang C, Liu Y W, Chi Z, et al. Ligand‐Activated Peroxisome Proliferator‐Activated Receptor β/δ Facilitates Cell Proliferation in Human Cholesteatoma Keratinocytes[J]. PPAR research, 2020, 2020(1): 8864813.
[5] Antonosante A, Castelli V, Sette M, et al. Neuroprotective effects of the PPARβ/δ antagonist GSK0660 in in vitro and in vivo Parkinson’s disease models[J]. Biological Research, 2023, 56.
[6] Capozzi M E, Savage S R, McCollum G W, et al. The peroxisome proliferator-activated receptor-β/δ antagonist GSK0660 mitigates retinal cell inflammation and leukostasis[J]. Experimental eye research, 2020, 190: 107885.
[7] Khan B, Chen M, Wang H, et al. GSK0660 enhances antitumor immunotherapy by reducing PD-L1 expression[J]. European Journal of Pharmacology, 2024, 972: 176565.
[8] Rubio B, Pintado C, Mazuecos L, et al. Central Actions of Leptin Induce an Atrophic Pattern and Improves Heart Function in Lean Normoleptinemic Rats via PPARβ/δ Activation[J]. Biomolecules, 2024, 14(8): 1028.
GSK 0660是一种强效的PPARβ拮抗剂，IC50值为155nM[1]。GSK 0660可通过抑制PPARβ的活性来阻止病理性血管生成和管状结构形成[1]。GSK 0660已被广泛用于调节P38 MAPK的激活并刺激角膜上皮细胞的迁移[3]。
在体外，5µM的GSK 0660处理胆脂瘤角质形成细胞24小时，导致细胞活力下降、PDK1表达受抑以及 AKT和GSK3β磷酸化水平降低[4]。0.2µM的GSK 0660处理SH-SY5Y细胞24小时，显著抑制了6-hydroxydopamine (6-OHDA)诱导的细胞死亡，阻止了氧化应激，并增加了SOD蛋白的活性[5]。10µM的GSK 0660处理人视网膜微血管内皮细胞(HRMECs)24小时，显著降低了TNF-α诱导的CCL8和CXCL10的表达，并减少了细胞粘附[6]。
在体内，每日腹腔注射20mg/kg剂量的GSK 0660，连续21天，显著抑制了CT-26异种移植小鼠模型中的肿瘤生长并降低了肿瘤重量[7]。每日腹腔注射1mg/kg剂量的GSK 0660，连续7天，可消除中枢注射瘦素对大鼠体重和食物摄入的影响，并显著增加血清胰岛素水平[8]。