M344 is a histone deacetylase (HDAC) inhibitor with an IC50 value of 100nM[1]. M344 exhibits potential for the treatment of Alzheimer's disease[2]. M344 effectively suppresses the growth and viability of various cancer cell types through multiple mechanisms[3-4].
In vitro, the addition of M344 (2.5–4μM) to HEK293 cells at 24 hours post-transfection during rAAV8 production significantly increased the genomic titer of recombinant adeno-associated virus[5]. Treatment of neuroblastoma cell lines SH-SY5Y, SK-N-BE(2), and KP-N-NS with M344 (1μM) for 12 hours markedly suppressed the mRNA and protein expression levels of c-Jun and Fra-1, while also reducing their phosphorylation activity[6].
In vivo, M344 (3–10mg/kg) was administered via intraperitoneal injection five days a week for 3-month-old Alzheimer's disease model mice for 4 months, which significantly improved their spatial memory and cognitive function[7].
References:
[1] Zhu M, Han Y, Gu T, et al. Class I HDAC inhibitors enhance antitumor efficacy and persistence of CAR-T cells by activation of the Wnt pathway. Cell Rep. 2024 Apr 23;43(4):114065.
[2] Jeong H, Shin S, Lee JS, et al. Pan-HDAC Inhibitors Promote Tau Aggregation by Increasing the Level of Acetylated Tau. Int J Mol Sci. 2019 Sep 1;20(17):4283.
[3] Yeung A, Bhargava RK, Ahn R, et al. HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation. Biomed Pharmacother. 2012 Apr;66(3):232-6.
[4] Knoche SM, Brumfield GL, Goetz BT, et al. The histone deacetylase inhibitor M344 as a multifaceted therapy for pancreatic cancer. PLoS One. 2022 Sep 20;17(9):e0273518.
[5] Scarrott JM, Johari YB, Pohle TH, et al. Increased recombinant adeno-associated virus production by HEK293 cells using small molecule chemical additives. Biotechnol J. 2023 Mar;18(3):e2200450.
[6] He W, Wu Y, Tang X, et al. HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells. Oncotarget. 2016 Feb 9;7(6):6727-47.
[7] Volmar CH, Salah-Uddin H, Janczura KJ, et al. M344 promotes nonamyloidogenic amyloid precursor protein processing while normalizing Alzheimer's disease genes and improving memory. Proc Natl Acad Sci U S A. 2017 Oct 24;114(43):E9135-E9144.