ML 9 hydrochloride

ML 9 hydrochloride is a selective protein kinase inhibitor. ML 9 hydrochloride inhibits the activity of Akt kinase, myosin light chain kinase (MLCK), and stromal interaction molecule 1 (STIM1), and induces autophagy by stimulating autophagosome formation^[1-2]. ML 9 hydrochloride can be used for research related to cancer, signal transduction, and autophagy mechanisms^[3-4].

In vitro, 3T3-L1 adipocytes were pretreated with ML 9 hydrochloride (100µM) for 20 minutes, followed by stimulation with insulin (33nM) for 14 minutes. ML 9 hydrochloride significantly inhibited insulin-induced 2-deoxyglucose transport activity and inhibited the translocation of glucose transporters (GLUT4 and GLUT1) from the intracellular space to the plasma membrane^[5]. HEK293 cells were treated with ML 9 hydrochloride (1–100µM) for 24 hours. ML 9 hydrochloride dose-dependently inhibited TRPC6 channel-mediated currents^[6].

In vivo, a burn injury BALB/c mouse model was administered ML 9 hydrochloride (2mg/kg; single injection ) via intraperitoneal injection. ML 9 hydrochloride significantly alleviated the burn-induced increase in intestinal permeability, intestinal mucosal tissue damage, and abnormal distribution of tight junction proteins (ZO-1, occludin, claudin-1), and reduced the phosphorylation level of myosin light chain (MLC) in the ileal mucosa^[7]. ML 9 hydrochloride (10µM; 25µL) was injected at the cervical-vaginal region of BALB/c AnNCr mice, followed by intravaginal inoculation with HPV16 pseudovirus (10⁶RLU/µL; 25µL). ML 9 hydrochloride significantly inhibited HPV16 infection in the mice^[8].

References:
[1] Ito S, Kume H, Honjo H, et al. ML-9, a myosin light chain kinase inhibitor, reduces intracellular Ca2+ concentration in guinea pig trachealis. Eur J Pharmacol. 2004 Feb 23;486(3):325-33.
[2] Shaikh S, Troncoso R, Mondaca-Ruff D, et al. The STIM1 inhibitor ML9 disrupts basal autophagy in cardiomyocytes by decreasing lysosome content. Toxicol In Vitro. 2018 Apr;48:121-127.
[3] Kondratskyi A, Yassine M, Slomianny C, et al. Identification of ML-9 as a lysosomotropic agent targeting autophagy and cell death. Cell Death Dis. 2014 Apr 24;5(4):e1193.
[4] Ribeiro D, Freitas M, Rocha S, et al. Calcium Pathways in Human Neutrophils-The Extended Effects of Thapsigargin and ML-9. Cells. 2018 Nov 9;7(11):204.
[5] Inoue G, Kuzuya H, Hayashi T, et al. Effects of ML-9 on insulin stimulation of glucose transport in 3T3-L1 adipocytes. J Biol Chem. 1993 Mar 5;268(7):5272-8.
[6] Shi J, Takahashi S, Jin XH, et al. Myosin light chain kinase-independent inhibition by ML-9 of murine TRPC6 channels expressed in HEK293 cells. Br J Pharmacol. 2007 Sep;152(1):122-31.
[7] Chen C, Wang P, Su Q, et al. Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury. PLoS One. 2012;7(4):e34946.
[8] Zhang Y, Liu W, He F, et al. Myosin 9 and N-glycans jointly regulate human papillomavirus entry. J Biol Chem. 2024 Feb;300(2):105660.

ML 9 hydrochloride是一种选择性蛋白激酶抑制剂，ML 9 hydrochloride可抑制Akt激酶、肌球蛋白轻链激酶（MLCK）和基质作用分子1（STIM1）的活性，并通过刺激自噬体形成诱导自噬^[1-2]。ML 9 hydrochloride可用于癌症研究、信号转导和自噬机制的相关研究^[3-4]。

在体外，ML 9 hydrochloride（100µM）预处理3T3-L1脂肪细胞20分钟，随后以胰岛素（33nM）刺激14分钟，ML 9 hydrochloride显著抑制胰岛素诱导的2-脱氧葡萄糖转运活性，抑制葡萄糖转运蛋白（GLUT4和GLUT1）从胞内空间向质膜的转位^[5]。ML 9 hydrochloride（1–100μM）处理HEK293细胞24小时，ML 9 hydrochloride能以剂量依赖性地抑制TRPC6通道介导的电流^[6]。

在体内，ML 9 hydrochloride（2mg/kg；单次）腹腔注射处理烧伤BALB/c小鼠模型，ML 9 hydrochloride显著减轻了烧伤诱导的小鼠肠道通透性增加、肠黏膜组织损伤以及紧密连接蛋白（ZO-1、occludin、claudin-1）的分布异常，并降低了回肠黏膜中肌球蛋白轻链（MLC）的磷酸化水平^[7]。ML 9 hydrochloride（10μM；25μL；单次）颈部阴道处注射至BALB/c AnNCr小鼠，随后对小鼠进行阴道注射HPV16病毒（10⁶RLU/μL；25μL）。ML 9 hydrochloride显著抑制了小鼠体内的HPV16感染^[8]。