Optimization of permeability in a series of pyrrolotriazine inhibitors of IRAK4.

Interleukin-1 receptor-associated kinase 4

IRAK-4,Renal carcinoma antigen NY-REN-64

RFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHE
NLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAF
TAKISDFGLARASEKFAQ(TPO)VM(TPO)(SEP)RIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHR
EPQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMT

RFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHE
NLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAF
TAKISDFGLARASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQLLLDIKEEI
EDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMT

RFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAMVDITTEELKQQFDQEIKVMAKCQHE
NLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSCLDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAF
TAKISDFGLARASEKFAQTVM(TPO)(SEP)RIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHREPQL
LLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKVQQLLQEMT

50 mM Hepes pH 7.5, 0.02% octylglucoside, 10% glycerol, 0.3 M NaCl, 1 mM TCEP

Interleukin-1 receptor-associated kinase 4 (E.C.2.7.11.1)

IRAK4, kinase, inhibitor, cancer, SIGNALING PROTEIN