SR-0813

SR-0813 is a potent and selective ENL/AF9 YEATS domain inhibitor. SR-0813 has IC50 and EC50 values of 25 nM and 205 nM for ENL YEATS domain, respectively. SR-0813 has IC50 and EC50 values of 311 nM and 76 nM (CETSA) for AF9 YEATS domain, respectively. SR-0813 binds MAP3K19 with over 100-fold lower affinity (Kd=3.5 μM) than ENL YEATS (Kd=30 nM). SR-0813 can be used for the research of acute leukemia[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

ENL YEATS domain:25 nM (IC50)

ENL YEATS domain:205 nM (EC50)

AF9 YEATS domain:311 nM (IC50)

AF9 YEATS domain:76 nM (EC50)

ENL YEATS domain:30 nM (Kd)

MAP3K19:3.5 μM (Kd)

SR-0813 (compound 10; 0, 1, 10 μM; 4 h) dose-dependent evicts ENL from known ENL binding sites, including the HOXA10 gene body and MYB promoter in MV4;11 cells[1]. SR-0813 (0, 1, 10 μM; 0, 24, 48, 72 h) downregulates the transcript levels of HOXA9, MEIS1, and MYC, and increases the abundance of the ITGAM transcript in MV4;11 cells[1]. SR-0813 (0, 1, 10 μM; approximately 2 weeks) inhibits the growth of multiple lineage leukemia (MLL)-fusion leukemia cell lines (MV4;11, MOLM-13, OCI/AML-2) and HB11;19 cells[1]. SR-0813 (1 μM, 4h) does not elicit global changes in gene expression in MV4;11 cells, but produces a strikingly selective suppression of ENL target genes[1]. Cell Proliferation Assay[1] Cell Line: MLL-fusion leukemia cell lines: MV4;11 (MLL-AF4 AML), MOLM-13 (MLL-AF9 AML), and OCI/AML-2 (MLL-AF6 AML), which are sensitive to the genetic loss of ENL. HB11;19 cells, which harboring an MLL-ENL fusion. Concentration: 0, 1, 10 μM Incubation Time: Approximately 2 weeks Result: Inhibited the growth of cells.

[1]. Garnar-Wortzel L, et al. Chemical Inhibition of ENL/AF9 YEATS Domains in Acute Leukemia. ACS Cent Sci. 2021 May 26;7(5):815-830.