Epigenetics Probes Collection

The study of post-translational modification (PTM) of lysine and/or arginine residues in histones and other proteins through methylation and acetylation has led to the discovery of three classes of epigenetic proteins:-

  1. Those which add a methyl or acetyl group (writers) using S-adenosylmethionine (methylation) and Acetyl-CoA (acetylation) as co-factors. Histone methyltransferases catalyze the transfer of up to three methyl groups to the e-amino group of a lysine residue or up to two methyl groups to the guanidine group of an arginine residue. In the case of arginine methylation, dimethylation can occur in a symmetrical or unsymmetrical manner.  Acetylation of lysine residues only occurs once and arginines are not acetylated.
  2. Those which remove a methyl or acetyl group (erasers).
  3. Those which bind histones/proteins containing a particular PTM (readers).

Each of these classes of epigenetic proteins contributes to the control of various genes and the goal of the Epigenetic Probes Project is to unravel the biology of these proteins by developing small-molecule inhibitors and antagonists with the following properties

  • IC50 or Kd < 100nM
  • Selectivity > 30-fold over proteins in the same family
  • Significant cellular activity at 1 microM

 Brochure - SGC Epigenetic Chemical Probes ( September 2016 )

 

Name Structure Protein Family Specific Targets Control In vivo parameters tested* Addedsort ascending
LLY-283
Methyltransferase PRMT5 LLY-284 07/16
A-395
Methyl Lysine Binder EED A-395N 07/16
TP-472
Bromodomains BRD9, BRD7 TP-472N yes 06/16
TP-064
Methyltransferase PRMT4 TP-064N 06/16
BAY-299
Bromodomains BRD1, TAF1 BAY-299N no 06/16
GSK864
Dehydrogenase Mutant isocitrate dehydrogenase 1 GSK990 yes 11/15
A-196
Methyltransferase SUV420H1/H2 A-197, SGC2043 no 07/15
GSK591
Methyltransferase PRMT5 SGC2096 no 07/15
MS023
Methyltransferase Type I PRMTs MS094 no 07/15
MS049
Methyltransferase PRMT4,6 MS049N no 06/15
NVS-CECR2-1
Bromodomains CECR2 no 06/15
I-BRD9
Bromodomains BRD9 no 05/15
BI-9564
Bromodomains BRD9, BRD7 yes 04/15
BAY-598
Methyltransferase SMYD2 BAY-369 yes 04/15
GSK484
Arginine deiminases PAD-4 GSK106 yes 03/15
GSK2801
Bromodomains BAZ2A, BAZ2B GSK8573 yes 12/14
LP99
Bromodomains BRD9, BRD7 2S,3R-enantiomer no 12/14
NI-57
Bromodomains BRPF1, BRPF2, BRPF3 no 12/14
PFI-4
Bromodomains BRPF1B no 12/14
OF-1
Bromodomains BRPF1, BRPF2, BRPF3 no 07/14
SGC707
Methyltransferase PRMT3 XY1 no 06/14
BAZ2-ICR
Bromodomains BAZ2A, BAZ2B yes 05/14
OICR-9429
WD40 WDR5 OICR-0547 no 05/14
GSK-LSD1
KDM LSD1 no 03/14
LLY-507
Methyltransferase SMYD2 SGC705 no 11/13
PFI-3
Bromodomains SMARCA,PB1 BDF25488524 no 11/13
A-366
Methyltransferase G9a, GLP no 06/13
UNC1999
Methyltransferase EZH2 UNC2400 yes 05/13
PFI-2
Methyltransferase SETD7 (S)-PFI-2 no 05/13
SGC-CBP30
Bromodomains CREBBP, EP300 BDOIA513 no 03/13
I-CBP112
Bromodomains CREBBP, EP300 no 03/13
Bromosporine
Bromodomains pan-Bromodomain no 01/13
UNC1215
Methyl Lysine Binder L3MBTL3 UNC1079 no 08/12
SGC0946
Methyltransferase DOT1L SGC0649 no 08/12
UNC0642
Methyltransferase G9a, GLP yes 08/12
GSK343
Methyltransferase EZH2 no 08/12
GSK-J1
use pro-drug GSK-J4 for cell assays
KDM JMJD3, UTX, JARID1B GSK-J2 (GSK-J5) no 07/12
IOX2
2OG PHD2 no 02/12
IOX1
KDM pan-2-OG no 01/12
PFI-1
Bromodomains BRD2, BRD3, BRD4, BRDT (BET) no 11/11
UNC0638
Methyltransferase G9a, GLP UNC0737 no 06/10
JQ1
Bromodomains BRD2, BRD3, BRD4, BRDT (BET) (-)-JQ1 yes 06/10
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