Fig. 1: SGC8158 is a potent and selective PRMT7 inhibitor in vitro.
From: Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response
a Structures of HTS hit compound SGC0911, potent compound SGC8172, active component of the chemical probe SGC8158 and its negative control SGC8158N. b SGC8158 inhibits PRMT7 in vitro with IC50 of <2.5 nM, whereas negative control compound SGC8158N has IC50 of 14 ± 2 μM, (n = 3 biological replicates, mean ± SEM). c SGC8158 is selective against a panel of 35 proteins, DNA, and RNA methyltransferases. IC50 values are represented by colored circles indicated top left of the panel. d Crystal structure of MmPRMT7 in complex with SGC8158. MmPRMT7 is shown in cartoon representation in cyan, hydrophobic pocket residues are shown in cyan sticks, and SGC8158 is in orange. The THW motif loop region is highlighted in red with dashed lines representing the unmodeled H313 and W314 residues. e For comparison, the crystal structure of MmPRMT7_SAH (PDB ID: 4C4A) is shown in cartoon representation in yellow, hydrophobic pocket residues are shown in yellow sticks, and SAH is in pink. The THW motif loop region is highlighted in green. f Comparison of the THW motif loop region of MmPRMT7_SGC8158 (in cyan) with that of PRMT5 (PDB ID: 5GQB) (in magenta), and PRMT1, 2, 3, 4, 6, and 8 (in gray) (PDB IDs: 1OR8, 5FUL, 2FYT, 2V74, 4Y30, and 5DST, respectively). SGC8158 is shown in orange sticks and SAH in gray sticks. Source data are provided as a Source Data file.
