SL-327 is a selective inhibitor of MEK1 and MEK2, with IC50 values of 0.18μM and 0.22μM, respectively[1]. SL-327 can be used to study the role of the MAPK signaling pathway in interictal spikes and behavior in epileptic rats[2]. SL-327 can penetrate the blood-brain barrier and produce neuroprotective effects in mice with ischemic brain injury[3].
In vitro, treatment of melanoma cells (MV3 and A375 cells) with SL-327 (1.25µM) for 48h restored the cell growth curve inhibited by TBMS1 treatment, restored the cell colony formation ability inhibited by TBMS1, and reversed the high expression levels of LC3B-II and p62 induced by TBMS1[4].
In vivo, SL-327 (20mg/kg) administered by intraperitoneal injection to male Swiss albino CD1 middle-aged mice blocked the positive effects of growth hormone (GH) on the mice in the radial arm maze test[5]. SL-327 (1, 5mg/kg) administered by intraperitoneal injection to Swiss mice followed by behavioral testing induced anxiolytic behavior in the mice, and the anxiolytic properties were particularly significant in combination with diazepam in the elevated plus maze (EPM) test[6].
References:
[1] Moranta D, Esteban S, García‐Sevilla J A. Acute, chronic and withdrawal effects of the cannabinoid receptor agonist WIN55212‐2 on the sequential activation of MAPK/Raf‐MEK‐ERK signaling in the rat cerebral frontal cortex: short‐term regulation by intrinsic and extrinsic pathways[J]. Journal of neuroscience research, 2007, 85(3): 656-667.
[2] Glazova M V, Nikitina L S, Hudik K A, et al. Inhibition of ERK 1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures[J]. Journal of neurochemistry, 2015, 132(2): 218-229.
[3] Wang X, Wang H, Xu L, et al. Significant neuroprotection against ischemic brain injury by inhibition of the MEK1 protein kinase in mice: exploration of potential mechanism associated with apoptosis[J]. The Journal of pharmacology and experimental therapeutics, 2003, 304(1): 172-178.
[4] Du J, Dong Z, Tan L, et al. Tubeimoside I inhibits cell proliferation and induces a partly disrupted and cytoprotective autophagy through rapidly hyperactivation of MEK1/2-ERK1/2 cascade via promoting PTP1B in melanoma[J]. Frontiers in cell and developmental biology, 2020, 8: 607757.
[5] Ramis M, Sarubbo F, Sola J, et al. Cognitive improvement by acute growth hormone is mediated by NMDA and AMPA receptors and MEK pathway[J]. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2013, 45: 11-20.
[6] Michalak A, Wnorowski A, Berardinelli A, et al. Diazepam and SL-327 synergistically attenuate anxiety-like behaviours in mice–Possible hippocampal MAPKs specificity[J]. Neuropharmacology, 2020, 180: 108302.
SL-327是MEK1和MEK2的选择性抑制剂，IC50值分别为0.18μM和0.22μM[1]。SL-327能够用于研究MAPK信号通路在癫痫大鼠发作间期棘波和行为中的作用[2]。SL-327能够穿透血脑屏障，在缺血性脑损伤小鼠中产生神经保护作用[3]。
在体外，SL-327（1.25µM）处理黑色素瘤细胞（MV3和A375细胞）48h，恢复了被TBMS1处理抑制的细胞生长曲线，恢复了被TBMS1抑制的细胞克隆形成能力，逆转了TBMS1诱导的LC3B-II和p62的高表达水平[4]。
在体内，SL-327（20mg/kg）通过腹腔注射处理雄性瑞士白化CD1中年小鼠，阻断了生长激素（GH）对小鼠在放射状迷宫测试中的积极作用[5]。SL-327（1, 5mg/kg）通过腹腔注射处理Swiss小鼠随后进行行为学测试，诱导了小鼠的抗焦虑行为，且与地西泮联合使用的抗焦虑特性在高架十字迷宫（EPM）测试中尤为显著[6]。