αC helix displacement as a general approach for allosteric modulation of protein kinases

► Allosteric targeting via displacement of helix αC is closely related to protein kinase inactivation. ► We highlight key allosteric pockets proximal to helix αC and discuss their relevance for drug discovery. ► Standing on recent structural data, three main allosteric pockets (MEK, PIF and ANS pockets) close to αC are discussed. ► We also highlight the relevance of targeting helix αC in the EGFR family of kinases. ► The analyses suggest that allosteric mechanisms in protein kinases may be more broadly conserved than initially thought.