TRPM4-IN-2 is a potent transient receptor potential melastatin 4 (TRPM4) inhibitor with an IC50 value of 0.16μM [1]. TRPM4-IN-2 binds in a pocket formed between the S3, S4, and TRP helices and the S4-S5 linker of TRPM4 to block the TRPM4 channel [2]. TRPM4-IN-2 has been widely used to decrease mouse TRPM4 currents and suppress arrhythmias [3].
In vitro, TRPM4-IN-2 treatment (100μM) for 48 hours significantly inhibited the proliferation of MDA-MB-231, A549 and KYSE30 cells [4]. Pre-treatment of HT22 cells with 10μM TRPM4-IN-2 for 2 hours significantly protected the cells from 5mM glutamate-induced cell death and disruption of cell integrity[5].
References:
[1] Stokłosa P, Borgström A, Hauert B, et al. Investigation of novel small molecular TRPM4 inhibitors in colorectal cancer cells[J]. Cancers, 2021, 13(21): 5400.
[2] Ekundayo B, Arullampalam P, Gerber C E, et al. Identification of a binding site for small molecule inhibitors targeting human TRPM4[J]. Nature communications, 2025, 16(1): 833.
[3] Hu Y, Cang J, Hiraishi K, et al. The role of TRPM4 in cardiac electrophysiology and arrhythmogenesis[J]. International Journal of Molecular Sciences, 2023, 24(14): 11798.
[4] Chang W, Gao W, Luo B, et al. Comprehensive insights into the role of TRPM4 in Pan-cancer progression and immune regulation[J]. ImmunoTargets and Therapy, 2025: 831-848.
[5] Bianchi B, Smith P A, Abriel H. The ion channel TRPM4 in murine experimental autoimmune encephalomyelitis and in a model of glutamate-induced neuronal degeneration[J]. Molecular brain, 2018, 11(1): 41.