RR6 is a potent, selective, reversible, competitive and orally active vanin inhibitor with an IC50 of 540nM for recombinant vanin-1[1]. Vanin is a membrane-bound pantetheinase that hydrolyzes pantetheine to cysteamine and regulates oxidative stress and inflammation[2]. RR6 is usually used in the studies of infection, inflammation and metabolism[3][4].
In vitro, RR6 (100µM; 30min) lowered intracellular Vanin-1 level and raised total GSH level in HepG2 cells[5].
In vivo, RR6 (3mg/mL; drinking water; 8 days) almost completely suppressed plasma vanin activity but did not alter hepatic steatosis, insulin sensitivity or glucose production in ZDF diabetic rats[6]. RR6 (3mg/mL; drinking water; 4 weeks) reduced neointima area and neointima/media ratio, and suppressed neointimal macrophage influx in Dark-Agouti-to-Brown-Norway rat aortic allografts[7].
References:
[1] Jansen PA, van Diepen JA, Ritzen B, et al. Discovery of small molecule vanin inhibitors: new tools to study metabolism and disease. ACS Chem Biol. 2013;8(3):530-534.
[2] Bartucci R, Salvati A, Olinga P, Boersma YL. Vanin 1: Its Physiological Function and Role in Diseases. Int J Mol Sci. 2019;20(16):3891.
[3] Schalkwijk J, Jansen P. Chemical biology tools to study pantetheinases of the vanin family. Biochem Soc Trans. 2014;42(4):1052-1055.
[4] Lv L, Wang T, Xie W, et al. Revealing VNN1: An Emerging and Promising Target for Inflammation and Redox Balance. Immun Inflamm Dis. 2025;13(10):e70274.
[5] Lu P, Zhang C, Fu L, et al. Near-Infrared Fluorescent Probe for Imaging and Evaluating the Role of Vanin-1 in Chemotherapy. Anal Chem. 2021;93(29):10378-10387.
[6] van Diepen JA, Jansen PA, Ballak DB, et al. Genetic and pharmacological inhibition of vanin-1 activity in animal models of type 2 diabetes. Sci Rep. 2016;6:21906.
[7] Wedel J, Jansen PA, Botman PN, Rutjes FP, Schalkwijk J, Hillebrands JL. Pharmacological Inhibition of Vanin Activity Attenuates Transplant Vasculopathy in Rat Aortic Allografts. Transplantation. 2016;100(8):1656-1666.
RR6 是一种强效、选择性、可逆、竞争性且具有口服活性的vanin抑制剂，对重组vanin-1的IC50为540nM[1]。Vanin是一种膜结合的泛酸酶，可将泛酸硫胺水解为半胱胺，并调控氧化应激与炎症[2]。RR6常用于感染、炎症及代谢相关研究[3][4]。
体外实验显示，RR6（100µM；30min）可降低HepG2细胞内Vanin-1水平并升高总GSH含量[5]。
体内实验中，RR6（3mg/mL；饮水给予；8天）几乎完全抑制ZDF糖尿病大鼠的血浆vanin活性，但并未改变肝脏脂肪变性、胰岛素敏感性或葡萄糖生成[6]。RR6（3mg/mL；饮水给予；4周）可缩小Dark-Agouti至Brown-Norway大鼠主动脉移植模型的新生内膜面积及新生内膜/中膜比值，并抑制新生内膜巨噬细胞浸润[7]。