Figure 5. Electronic model of selectivity.
Star 27-des methyl (PKC412-relevant) and Star 27 are depicted in 3D with electron potential mapping (EPM) to highlight the difference of a single methyl group. (A–C) Star 27-des methyl maintains a partial positive charge at the C7 position which matches the partial negative charge on the Thr 670 gatekeeper of KIT, potentially explaining PKC412's relative affinity for KIT. (D–F) Star 27 maintains a neutral charged surface at C7 due to the presence of the methyl group, potentially explaining its lack of binding to KIT.