MG 149 is an inhibitor of histone acetyltransferases (HAT) with IC50 values of 74μM and 47μM for Tip60 and MOF, respectively[1].
In vitro, treatment with 2μM MG 149 for 12h prevented H4K16 acetylation in response to DNA damage induced by doxorubicin in serum-deprived A549 and U2OS[2]; Treatment with 100μM MG 149 for 30min significantly prevented UV-induced XPF acetylation in Hela[3]. In the dose range of 0-30μM, MG 149 treatment for 20h inhibited the catalytic activity of TIP60 in wild-type 2D10 cells in a dose-dependent manner and reversed the HIV latent state[4].
In vivo, 1mg/kg MG 149 administered via intraperitoneal injection could relieve HDM-induced Airway Hyperresponsiveness (AHR) and airway inflammation in murine allergic asthma models[5]. MG 149 administered via intraperitoneal injection at a dose of 1.6mg/kg for 14 days blocked the increased glutamate release in ventral hippocampal CA1 (vCA1) after electrical stimulation in dorsomedial prefrontal cortex (dmPFC) of CRS mice[6].
References:
[1] Ghizzoni M, Wu J, Gao T, Haisma HJ, Dekker FJ, George Zheng Y. 6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site. Eur J Med Chem. 2012 Jan;47(1):337-44.
[2] García-González R, Morejón-García P, Campillo-Marcos I, Salzano M, Lazo PA. VRK1 Phosphorylates Tip60/KAT5 and Is Required for H4K16 Acetylation in Response to DNA Damage. Cancers (Basel). 2020;12(10):2986.
[3] Wang J, He H, Chen B, et al. Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and activation. Nat Commun. 2020;11(1):786.
[4] Li Z, Mbonye U, Feng Z, et al. The KAT5-Acetyl-Histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency. PLoS Pathog. 2018;14(4):e1007012.
[5] Liu Y, Du J, Liu X, et al. MG149 inhibits histone acetyltransferase KAT8-mediated IL-33 acetylation to alleviate allergic airway inflammation and airway hyperresponsiveness. Signal Transduct Target Ther. 2021;6(1):321.
[6] Wang Y, Xia M, Lu J, et al. TIP60 mediates stress-induced hypertension via promoting glutamatedmPFC-to-vCA1 release. Clin Exp Hypertens. 2023;45(1):2259130.
MG 149是一种组蛋白乙酰转移酶（HAT）抑制剂，对Tip60和MOF的IC50值分别为74μM和47μM[1]。
体外实验中，2μM MG 149处理12小时，可抑制血清饥饿的A549和U2OS细胞中由doxorubicin诱导的DNA损伤引起的H4K16乙酰化水平[2]。100μM MG 149处理30分钟，可显著抑制HeLa细胞中紫外诱导的XPF乙酰化[3]。在0-30μM的剂量范围内，MG 149处理20小时后，以剂量依赖的方式抑制野生型2D10细胞中TIP60的催化活性，并逆转HIV潜伏状态[4]。
体内实验中，腹腔注射1mg/kg的MG 149可缓解由HDM诱导的小鼠过敏性哮喘模型中的气道高反应和气道炎症[5]。腹腔注射1.6mg/kg的MG 149连续14天，可阻断CRS小鼠背内侧前额叶皮（dmPFC）电刺激后腹侧海马（vCA1）中谷氨酸释放的增加[6]。