BRD7116, a bis-aryl sufone, acts as a selective inhibitor of leukemia stem cell activity by directly acting on the stromal cells to inhibit cobblestone formation [1,2].
BRD7116 displayed cell-non-autonomous anti-leukemia activity. In leukemia stem cells isolated from the bone marrow of leukemic animals in co-culture, BRD7116 exhibited an EC50 of 200 nM. BRD7116 displayed limited activity against normal HSPCs and AML cell lines with EC50s about 20 μM. BRD7116 showed activity against patient-derived primary human leukemia cells. Treatment of LSCe cells with BRD7116 induced transcriptional changes. The mechanism by which BRD7116 impaired the stroma’s ability to support leukemia cells has remained an important issue for future determination [1].
References:
[1] Hartwell K A, Miller P G, Mukherjee S, et al. Niche-based screening identifies small-molecule inhibitors of leukemia stem cells[J]. Nature chemical biology, 2013, 9(12): 840-848.
[2] Sachlos E, Kerstetter-Fogle A. Research Highlights: Highlights from the latest articles in regenerative medicine[J]. Regenerative medicine, 2014, 9(2): 145-147.