KZ-001 is a highly potent and selective MEK1/2 inhibitor with IC50 values of 7.4/64 nM, respectively, exhibits greater inhibition against BRAF- and KRAS-mutant tumor cells than AZD6244.
KZ-001 has approximately 27-fold stronger activity than AZD6244.
KZ-001 (1 nM to 625 nM) inhibits cellular ERK phosphorylation in A375, Calu-6, Colo-205 and HT-29 cells.
KZ-001 shows much more potent inhibition of proliferation, with an IC50 of 2.9-5.7 nM and 169.9 nM for the BRAFV600E and KRASQ61K cancer cell lines, compare with AZD6244, the RAFWT and RASWT cell lines A431 are resistant to KZ-001.
KZ-001 induces apoptosis in Colo-205 and Calu-6 cells, but not RAFWT and RASWT cell lines. KZ-001 (3 mg/kg and 6 mg/kg) completely inhibits the growth of Colo-205 tumors (TGI 103.9% and 108.8%, respectively; p < 0.01).
KZ-001 shows synergistic effect against BRAF mutant cell lines in vitro and in vivo, when combined with vemurafenib and docetaxel.