Figure 4.

(A) Discovery and design procedure of the TRK inhibitor, larotrectinib, by combing Scintillation Proximity Assay and medicinal chemistry and (B) X-ray cocrystal structure of TRKA with the R-enantiomer of compound 3 (PDB ID: 4YNE, 2.0 Å). The kinase is illustrated with green ribbons, and the hydrogen bonds are depicted in black dashed lines. Compound atoms are in different colors: C, orange; N, blue; F, light cyan.