EPZ020411 (dihydrochloride)

EPZ020411 dihydrochloride is a selective, blood-brain barrier-permeable PRMT6 inhibitor with an IC₅₀ of 0.010 μM. EPZ020411 dihydrochloride blocks PRMT6-mediated histone H3R2 methylation, reduces ROS production, and inhibits Apoptosis. EPZ020411 dihydrochloride is applicable to research related to neuropathic pain, colorectal cancer, ototoxicity, hearing loss and glioblastoma^{[1][2][3][4][5]}. In Vitro:EPZ020411 dihydrochloride potently inhibits purified PRMT6 enzyme with an IC₅₀ of 0.010 μM, and exhibits over 100-fold selectivity against a variety of other arginine methyltransferases^[1].
EPZ020411(at concentrations greater than 0.01 μM for 48 h) dihydrochloride inhibits PRMT6-mediated H3R2me2a modification in PRMT6-overexpressing A375 cells, with an IC₅₀ of 0.637 ± 0.241 μM^[1].
EPZ020411 (1-1000 μM; 24 h) dihydrochloride reduces the viability of BV2 microglial cells at concentrations of 50, 100 and 1000 μM, while concentrations of 1, 10 and 20 μM do not alter cell viability^[2].
EPZ020411 (2-4 μM; 14 days) dihydrochloride reduces the cell viability of HCT116, HT29, SW480, MC38 and CT26 colorectal cancer (CRC) cell lines, with the maximal effect observed at 4 μM^[3].
EPZ020411 (40 μM) dihydrochloride protects hair cells in postnatal day 2 mouse cochlear explants from cisplatin-induced death and significantly increases hair cell survival rates across all cochlear turns^[4].
EPZ020411 (20-40 μM; 48 h) dihydrochloride potently inhibits the invasive ability of human glioblastoma U87 and LN229 cells in a concentration-dependent manner^[5]. In Vivo:EPZ020411 (10 mg/kg; intrathecal injection; 1 h before CCI) dihydrochloride attenuates CCI-induced neuropathic pain, microglial activation, neuroinflammation and glycolysis in the spinal dorsal horn of mice^[2].
EPZ020411 (10 mg/kg; i.p.; once daily; for 3 consecutive weeks) dihydrochloride significantly inhibits the growth of subcutaneous CT26 MSS colorectal cancer xenografts in BALB/c mice^[3].
EPZ020411 (10 mg/kg; i.p.; daily; for 5 consecutive weeks) dihydrochloride slightly reduces the tumor burden of microsatellite-stable colorectal cancer induced by AOM/DSS in C57BL/6 mice^[3].
EPZ020411 (administered via transtympanic route; single dose) dihydrochloride significantly attenuates neomycin-induced chronic hearing loss in 5-day-old C57BL/6 mice and protects the survival of hair cells in the middle and basal turns of the cochlea^[4]
EPZ020411 (10 mg/kg; i.p.; single administration) dihydrochloride significantly attenuates acute hearing loss induced by neomycin combined with furosemide in 28-day-old C57BL/6 mice, maintains hair cell survival, and inhibits cochlear cell apoptosis and reactive oxygen species production^[4].