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. 2016 Jul 11;37(10):1273–1280. doi: 10.1038/aps.2016.64

Table 1. The profiles of small molecule inhibitors of histone lysine methyltransferases (HKMTs).

Compound Target HKMTs Mechanism Biochemical potency (IC50) Cellular potency (IC50) In vivo activity Fold selectivity Status Reference
graphic file with name aps201664i1.jpg EHMTs Substrate competitive 1.9±0.1 μmol/L (EHMT2) 0.7±0.1 μmol/L (EHMT1) 500±43 nmol/L (MDA-MB-231) No No inhibition observed (other HMTs) Preclinical 31,32,33
graphic file with name aps201664i2.jpg EHMTs Substrate competitive <15 nmol/L (EHMT2) 19±1 nmol/L (EHMT1) 81±9 nmol/L (MDA-MB-231) No ∼500 (other HMTs) Biological testing 30,33
graphic file with name aps201664i3.jpg EHMTs Substrate competitive 0.006 μmol/L (EHMT2) 0.026 μmol/L (MDA-MB-231) No No report Biological testing 34
graphic file with name aps201664i4.jpg EHMTs Substrate competitive 0.004 μmol/L (EHMT2) 0.025 μmol/L (MDA-MB-231) No No report Biological testing 34
graphic file with name aps201664i5.jpg EHMTs Unknown 1.6 μmol/L (EHMT2) 1.5 μmol/L (EHMT1) No No ∼100 (other 3 HMTs) Biological testing 35
graphic file with name aps201664i6.jpg EZH2 SAM competitive 54±5 nmol/L (EZH2-PRC2) 80±30 nmol/L (OCI-LY19 EZH2WT) No ∼50 (EZH1) >500 (other 15 HMTs) Preclinical 40
graphic file with name aps201664i7.jpg EZH2 SAM competitive 11±5 nmol/L (EZH2) 2–38 nmol/L (EZH2 mutants) 8 nmol/L (OCI-LY19, EZH2WT), 2–90 nmol/L (EZH2 mutants) Yes ∼35 (EZH1) >4500 (other HMTs) Phase II 51
graphic file with name aps201664i8.jpg EZH2 SAM competitive 9.9 nmol/L (EZH2) 28–861 nmol/L (DLBCL, EZH2 mutants) Yes ∼150 (EZH1) ∼1000 (other 20 HMTs) Phase I 49
graphic file with name aps201664i9.jpg EZH2 SAM competitive 4 nmol/L (EZH2) 174±84 nmol/L (HCC1806) No ∼60 (EZH1) ∼1000 (other HMTs) Preclinical 48
graphic file with name aps201664i10.jpg EZH2 SAM competitive 15±2 nmol/L (EZH2WT) 13±3 nmol/L (EZH2Y641F) ∼370 nmol/L (SU-DHL6, EZH2Y641N) No ∼90 (EZH1) >10 000 (other HMTs) Biological testing 50
graphic file with name aps201664i11.jpg EZH2 SAM competitive <10 nmol/L (EZH2) 124±11 nmol/L (MCF10A, EZH2WT) Yes ∼10 (EZH1) ∼10000 (other HMTs) Preclinical 47
graphic file with name aps201664i12.jpg DOT1L SAM competitive 38 nmol/L (Cpd 4) 120 nmol/L (Cpd 5) 110 nmol/L (Cpd 6) No No >29 (other 4 HMTs) Biological testing 21
graphic file with name aps201664i13.jpg DOT1L SAM competitive 0.4±0.1 nmol/L 0.17–6.47 μmol/L (MLL-rearranged leukemia cell lines) Yes >1000 (other HMTs) Preclinical 22
graphic file with name aps201664i14.jpg DOT1L SAM competitive Ki=0.08±0.03 nmol/L 3.5±0.7 nmol/L (MV4-11) Yes >37 000 (other 15 HMTs) Phase I 23
graphic file with name aps201664i15.jpg SMYD2 Substrate competitive <15 nmol/L (p53) 31 nmol/L (H4) 0.6 μmol/L (U2OS) 0.6 μmol/L (KYSE-150) No >100 (other 25 HMTs and non-HMTs) Biological testing 56
graphic file with name aps201664i16.jpg SMYD2 Substrate competitive 0.12 μmol/L No No >700 (6 other HMTs) Biological testing 59
graphic file with name aps201664i17.jpg SMYD2 Substrate competitive 2.8 nmol/L 42% reduction of p53K370me1 (A549) No No significant inhibition (>50%) at 1 μmol/L for other 30 HMTs Biological testing 60