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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: Expert Opin Investig Drugs. 2016 Feb 16;25(3):335–358. doi: 10.1517/13543784.2016.1144747

Table 3.

PRMT3-specific inhibitors.

Structure and numbering Activity year[ref]
Biochemical
graphic file with name nihms794708t13.jpg Assay: SAHH-coupled assay; SPA; RFA

  1. IC50 1.6 μM (with H4-24 peptide as substrate), 2 μM (with rpS2 protein as substrate); Kd = 9 μM; inactive to five HKMTs (G9a, EHMT1, SUV39H2, SETD7, and SETD8), three PRMTs (-1, -4, and -8), weakly inhibit PRMT5;

  2. Allosteric binding, crystal structure available;

  3. Not metabolically stable enough for cell-based assays;


Note: all the methylation assays were done under balanced condition.		 2012[96]
graphic file with name nihms794708t14.jpg Assay: SPA; RFA
19a:

  1. IC50 0.48 μM on PRMT3; 40-fold selective for PRMT3 over G9a, GLP, and SUV39H2; totally inactive against PRMT5, SETD7, PRC2, SETD8, SETDB1, SUV420H1, SUV420H2, MLL1, SMYD3, SMYD2, DOT1L, and DNMT1;

  2. Crystal structure available.

 2013[80]
graphic file with name nihms794708t15.jpg Biochemical Cellular & Animal model
Assay: SPA

  1. IC50 0.03 μM (PRMT3); outstanding selectivity against 31 HKMTs, PRMTs, DNMTs and RNA-methyltransferase as well as 250 non-epigenetic proteins;

  2. Crystal structure available;

  3. Kd = 0.053 μM and 0.085 μM, determined by ITC and SPR assay, respectively.

  1. Bind with PRMT3 overexpressed in HEK293 and A549 cells (EC50 = 1.3 μM and 1.6 μM, respectively) determined by InCELL Hunter assay;

  2. Inhibit endogenous and exogenous H4R3me2a with (IC50 = 0.225μM and 0.091μM, respectively) from western blot;

  3. No toxicity at 24h;

  4. In vivo PK: The plasma level at 6 h post injection was 208 nm, more than 2-fold higher than its IC50 value in the cellular assay and the half-life was about 1 h.

 2015[97]