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. Author manuscript; available in PMC: 2020 Jul 14.
Published in final edited form as: Cell. 2016 Sep 15;167(1):171–186.e15. doi: 10.1016/j.cell.2016.08.057

Figure 2. High-Throughput Screening and Medicinal Chemistry Identifies ML390 as an Inducer of Myeloid Differentiation.

Figure 2.

(A and B) In (A), upon differentiation (following the removal of estradiol), Lys-GFP-ER-HoxA9 GMPs upregulate GFP fluorescence and (B) the cell-surface markers CD11b and Gr-1.

(C) A high-throughput flow cytometry phenotypic screen was established to identify compounds that could trigger differentiation of Lys-GFP-ER-HoxA9 cells as monitored by the upregulation of GFP and CD11b.

(D) Twelve biologically active compounds were identified, including compound 3 (C03) and compound 7 (C07).

(E) The most potent small molecule was a derivative of (R)-C07, designated ML390.

(F) C03 and (R)-C07 triggered myeloid differentiation, while (S)-C07 lacked activity.

(G) ML390 is capable of causing myeloid differentiation in murine (ER-HoxA9) and human (U937 and THP1) AML models.

(H) Imaging flow cytometry demonstrates upregulation of GFP and CD11b expression as well as the downregulation of KIT expression in Lys-GFP-ER-HoxA9 cells during differentiation in the absence of estradiol (-E2) or as the result of treatment with ML390.

See also Figure S2.