COMMENT SGC-iMLLT was developed based on a low micromolar MLLT1 YEATS domain inhibitor which was identified in a medium throughput screening campaign using AlphaScreen technology. Docking studies utilizing an available crystal structure of MLLT1:H3Kac27 peptide (PDB ID 5J9S) guided the design approach and medicinal chemistry efforts to yield SGC-iMLLT including extensive SAR studies (>200 derivatives). SGC-iMLLT is a selective inhibitor of the YD of MLLT-1 and -3 with no observed off-target activity against related acyllysine reading domains (10 µM compound concentration, AlphaScreen) and 48 recombinant human bromodomain proteins (50 µM compound concentration, thermal shift assay). The binding mode of SGC-iMLLT to MLLT1 YD was deciphered using X-ray crystallography (PDB ID 6HT1) confirming its interaction with the Kac/Kcr binding site of MLLT1 YD. Target engagement was demonstrated by CETSA (MV-4-11 cells, MLLT1) as well as FRAP (U2OS cells transfected with GFP‐tagged MLLT1 and MLLT3), and NanoBRET (HEK293 cells, MLLT3) studies. Moreover, SGC-iMLLT reduces MYC, DDN expression while it increases CD86 expression in MV-4-11 AML. Metabolic stability of SGC-iMLLT was investigated in primary human hepatocytes demonstrating moderate metabolic resistance (t1/2 53 min). The primary metabolic process was determined to be N-demethylation. However, SGC-iMLLT was not used in in vivo studies. SGC-iMLLT is structurally similar to NVS-MLLT-1. Apr 19 2021 - 11:48am

DESCRIPTION SGC-iMLLT is a first-in-class chemical probe and a potent, selective inhibitor of MLLT1/3-histone interactions with an IC50 of 0.26 ¦ÌM. SGC-iMLLT shows high binding activity towards MLLT1 YEATS domain (YD) and MLLT3 YD (AF9/YEATS3) with Kds of 0.129 and 0.077 ¦ÌM, respectively[1].

PRICE 110

DESCRIPTION SGC-iMLLT is a potent and selective MLLT1/3-histone interactions inhibitor(IC50 = 0.26 ??M),and is a first-in-class chemical probe displaying cellular target engagement of MLLT1(Kd = 0.129???M) and MLLT3(Kd = 0.077???M).

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION SGC-iMLLT is a potent and selective MLLT1/3-histone interactions inhibitor(IC50 = 0.26 μM),and is a first-in-class chemical probe displaying cellular target engagement of MLLT1(Kd = 0.129 μM) and MLLT3(Kd = 0.077 μM). (TargetMol Bioactive Compound Library)