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X-ray cocrystal structure of TRKA with the R-enantiomer of 14. The protein adopts the DFG-in conformation. Compound 14 maintains the key hydrogen bond between the hinge NH of Met592 and N1 of imidazopyridazine. Surprisingly, the imidazopyridazine is now flipped. This allows for the fluorophenyl group to better fit the ribose binding pocket compared to 10. Color coding according to Figure 1.
