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. Author manuscript; available in PMC: 2024 Dec 7.
Published in final edited form as: Mol Cell. 2023 Nov 9;83(23):4304–4317.e8. doi: 10.1016/j.molcel.2023.10.028

Figure 4. SAC is a selective substrate-competitive inhibitor of YTHDF1.

Figure 4

(A) Illustration of YTHDF1 inhibition in FMRP-deficient neurons to treat FXS.

(B) Chemical structure of a YTHDF1 inhibitor salvianolic acid C (SAC).

(C) IC50 value of SAC against YTHDF1 and YTHDF2 measured by AlphaScreen experiments. The selectivity of SAC between YTHDF1 and YTHDF2 is around 20:1.

(D) NMR CPMG binding assay between SAC and YTHDF1. The measurements were conducted under the conditions of 0 μM (red), 5 μM (green), 10 μM (blue) and 20 μM (purple) YTHDF1 protein, respectively.

(E) Competitive binding analysis between SAC and m6A-containing RNA oligos. The activities of SAC were summarized in the table, in which m6A-containing RNA oligos were shown as m6A. (Data are expressed as the mean ± se).