Extended Data Fig. 3: Binding pocket of RET. | Nature Cancer

Extended Data Fig. 3: Binding pocket of RET.

From: Vepafestinib is a pharmacologically advanced RET-selective inhibitor with high CNS penetration and inhibitory activity against RET solvent front mutations

Extended Data Fig. 3

(a) X-ray crystal structure shows that TAS compound 1 fits into a pocket surrounded by L730, G731, F735, V738 and L881. (b) View from the gatekeeper residue (V804) in the X-ray structure of the RET-TAS compound 1 complex. TAS Compound 1 is shown as a stick model in yellow. (c) Crystal structures of human RET complexed with TAS compound 1, selpercatinib or pralsetinib. In all three structures, RET showed the active conformation; DFG-in, αC helix-in, Activation Segment-out, and R spine-liner. Therefore, the three drugs can potentially be classified as type I inhibitors.

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