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. Author manuscript; available in PMC: 2020 Oct 2.
Published in final edited form as: J Am Chem Soc. 2019 Sep 20;141(39):15700–15709. doi: 10.1021/jacs.9b08660

Figure 2: Steps toward potent TAM back-pocket binders.

Figure 2:

A, Growing the aryl-alkyne-aryl spacer: template compound 1 (green), aryl-alkyne and aryl FRASEs (magenta), and TAM/FLT3 profiles of inhibitors (IC50 values given in nM) with a partial (2) and full (3) spacers. B, Filling the back-pocket by aromatic groups: template compound (green), source FRASEs (magenta) and sample inhibitors 4–6 not showing sufficient potency and selectivity. C, Filling the back-pocket with smaller aliphatic groups: template compound (green), source FRASEs (magenta) and sample inhibitors 7, 8 showing high potency and promising selectivity. D, Co-crystal structure of 7 in complex with MERTK and its major interactions with the adenine pocket (Pro672, Phe673 and Glu595) and back-pocket (Lys619).