Development of a New MEK Inhibitor KZ-02
(A) Chemical structure of KZ-02 and AZD6244.
(B) KZ-02 structure (purple) overlapped with AZD6244 (yellow) with the co-crystal structure of MEK1/ATP/AZD6244 (PDB code: 4U7Z) as the model. KZ-02 shows similar binding with MEK1, and key residues of MEK1 that are important for interaction with KZ-02/AZD6244 are shown.
(C) In vitro kinase inhibition assay determines IC50 for AZD6244 to 5.09 nmol/L.
(D) In vitro kinase inhibition assay determines IC50 for KZ-02 to be 1.07 nmol/L. Data are represented as mean ± SD.