GSK3368715 dihydrochloride is a potent, reversible type I PRMT inhibitor with anti-tumor effects in human cancer models[1]. GSK3368715 decrease the PRMT1-specific histone mark H4R3me2a without affecting the methylation of H3R17me2a (by CARM1 and PRMT6) or PABP1 (by CARM1)[3].
In vitro, treatment with 6µM GSK3368715 for 24 hours inhibited cGAS methylation levels in HEK293T cells[1]. Treatment with 6μM GSK3368715 for 48 hours increased the phosphorylation level of IRF3 in HeLa cells expressing wild-type cGAS[1]. The growth half-maximal inhibitory concentration (gIC50) values of GSK3368715 against MM cell lines ranged from 0.021µM to 14.405µM[2]. GSK3368715 at concentrations ranging from 0.12 to 1μM reduced colony growth in a dose-dependent manner when MDA-MB-468 cells were cultured on plastic for 9 days[3].
In vivo, oral administration of GSK3368715 at 80mg/kg once daily for 14 days resulted in elevated mPD-L1 expression across multiple organs and tissues in six-weeks old BALB/c female mice[1]. Treatment with GSK3368715 (80mg/kg; orally; once daily for 5 days) in nude mice bearing MDA-MB-468–derived xenografts led to increased global monomethylation, decreased H4R3me2a levels in tumors, and a significant delay in tumor growth[3].
References:
[1] Liu J, Bu X, Chu C, et al. PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity. Nat Commun. 2023;14(1):2806.
[2] Hussain T, Awasthi S, Shahid F, Yi SS, Sahni N, Aldaz CM. Therapeutic potential of PRMT1 as a critical survival dependency target in multiple myeloma. BMC Cancer. 2025;25(1):1704.
[3] Suresh S, Huard S, Brisson A, et al. PRMT1 Regulates EGFR and Wnt Signaling Pathways and Is a Promising Target for Combinatorial Treatment of Breast Cancer. Cancers (Basel). 2022;14(2):306.