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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 7.

Other PRMT inhibitors.

Structure and numbering Activity year[ref]
Biochemical Cellular
1) Promiscuous PRMT inhibitors
graphic file with name nihms794708t29.jpg Assay: RFA; western blot; RGA
Compound 55: IC50 112μM (PRMT1); similar activity to AMI-1 against PRMT-1,-3 and -4;
Compound 56: IC50 272 μM (PRMT1)
Note: IC50 of AMI-1 was 92 μM (PRMT1)		 Compound 55: Inhibition on methylation of transiently transfected Npl3p start to show at 50 μM 2010[73]
graphic file with name nihms794708t30.jpg Assay: ELISA
IC50 6.1 μM (PRMT1);
15% – 20% inhibition on PRMT5 (@ 100 μM)		 Dose-dependent inhibitory effect on the expression level of androgen-dependent genes (TMPRSS2 and FKBP5); 50% of the maximum inhibition was achieved at 25μM. 2013[102]
graphic file with name nihms794708t31.jpg Assay: RGA
Better activity than AMI-1 on PRMT1, -3, -4, -5, -6 and -8;
IC50 4.2 μM (PRMT1);
IC50 2.7 μM (CARM1);
Inactive on SET7/9

  1. Inhibit H3R17 methylation to 55% (@100 μM) and 35% (@300 μM), compared with around 80% by AMI-1 of the same concentration;

  2. Inhibit secretion of IFNγ by Th1 cells (starting @ 10μM) and IL-4 by Th2 cells (starting @ 0.1μM);

  3. No effect on viability of Th cells

  4. Interfere with IL-4 expression at transcription level;

  5. Interrupt association of PRMT1 and NIP45.

 2010[74]
2) Bisubstrate inhibitors
graphic file with name nihms794708t32.jpg Assay: RGA
IC50 3–6 μM (PRMT1); IC50 > 100 μM (CARM1); IC50 > 100 μM (SET7/9)		 — 2010[75], 2011[76]
graphic file with name nihms794708t33.jpg Assay: ELISA
IC50 of compound 61 and 62: IC50 0.1–0.2 μM (CARM1); > 5 μM (PRMT1, PRMT6);
IC50 of compound 63: 3.2 μM (PRMT6); > 50 μM (PRMT1, CARM1)		 — 2015[103]
graphic file with name nihms794708t34.jpg Assay: SPA
IC50 6 μM (PRMT5/PRMT7); inactive to other PRMTs
Note: all the methylation assays were done under balanced condition		 Start to decrease the methylation level of SmD and SmB proteins in MBMDA231 cells at 10 μM. 2015[101]
3) Inhibitors with substrate-targeting property
graphic file with name nihms794708t35.jpg Assay: RFA; western blot
Bind histone H3 instead of CARM1 as determined by ITC, targeting residue sequence KAPRK
Specifically inhibit methylation of H3R17 by CARM1 (IC50 around 25 μM); no effect to acetylation of H3K14 and H3K18 by p300.		 Affect H3R17 methylation but not H3K14 and H3K18 acetylation in HeLa cells;
Repress the expression of p53-responsive gene, p21, by decreasing H3R17 methylation		 2010[88]
graphic file with name nihms794708t36.jpg Assay: RFA
Compound 66:
IC50 12 μM (PRMT1 with H4(1-20) peptide), 7.1 μM (PRMT3 with R4 peptide), 2 mM (CARM1 with H3(1-31) peptide), 39 μM (PRMT6 with H3(1-31) peptide), 21 μM on (p300 with H4(1-20) peptide)
Bind H4(1-20) peptide as validated by uv, fluorescence and mass spectra .
Note: : IC50 of AMI-1 is 137 μM on PRMT1 with H4(1-20) peptide as substrate		 — 2010[139]
graphic file with name nihms794708t37.jpg Assay: RFA
Compound 68: IC50 41 μM (PRMT1 with H4(1-20) peptide)
Compound 69:

  1. IC50 12 μM (PRMT1 with H4(1-20) peptide), 15 μM (p300 with H4(1-20) peptide;

  2. Targeting peptide as determined by fluorescence spectrum


Note: : IC50 of AMI-1 is 77 μM on PRMT1 with H4(1-20) peptide as substrate		 Compound 68:
10 μM achieve 70% inhibition on proliferation of LNCaP C-81 Cells at in regular medium and 30% inhibition in steroid-reduced condition		 2012[242]