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. Author manuscript; available in PMC: 2023 Aug 19.
Published in final edited form as: ACS Chem Biol. 2022 Jul 14;17(8):2188–2200. doi: 10.1021/acschembio.2c00330

Figure 5. Top enhancers of both rat and mouse OPC differentiation inhibit EBP and sterol 14-reductase.

Figure 5.

(A) Validated screening hits from Deshmukh et al., 2013 and Lariosa-Willingham et al., 2016 with annotations of subsequently-established inhibitory activity for EBP, CYP51, or sterol 14-reductase. (B), (D) Percentage of MBP+ oligodendrocytes generated from OPCs following treatment with bioactive small molecules. OPCs in (B) were treated with compounds at a uniform dose of 1.5 μM while those in (D) were treated in dose response as shown. n=4 wells per condition, except DMSO, amorolfine and TASIN-1, n=8 wells, with >1,000 cells analyzed per well. (C), (E) GC-MS based quantification of 14-dehydrozymostenol, zymostenol, and zymosterol levels in OPCs treated for 24 h with the indicated screening hits at their effective concentrations. n=2 wells per condition. (F) Percentage of MBP+ oligodendrocytes in OPCs treated with vanoxerine in dose response as shown. (G), (H), (I) GC-MS based quantification of zymostenol, zymosterol, and 14-dehydrozymostenol in OPCs treated with vanoxerine and donepezil in dose response for 24 h. n=2 wells per condition. Results in (D) represent two independent experiments. For percentage of MBP+ oligodendrocytes for all bioactive small molecules that were screened, see Fig. S4. S14R, sterol 14-reductase.