DKFZ-251 is a kininogenase-related peptidase KLK6 inhibitor ( IC50 =0.47 μM), and also exhibits certain inhibitory activity against KLK5 and KLK7 ( IC50 values are 1.1 nM and 73 nM, respectively). DKFZ-251 transiently acylates the catalytic serine of KLK6 to form a long-lived acyl-enzyme complex that inhibits enzyme function. DKFZ-251 is a phenotypic modulator that alters cell proliferation capacity and regulates epithelial-mesenchymal transition (EMT). DKFZ-251 can be used in research related to head and neck cancer [1].
In Vitro, DKFZ-251 (compound 11) (200 μM; 1 h) forms a long-lived acyl-enzyme complex with recombinant triple-mutant KLK6, with a half-life of 6.43 h[1]. DKFZ-251 (100-500 nM; 48 h) induces a dose-dependent increase in BrdU incorporation and causes phenotypic changes in FaDu cells, which is consistent with the targeted inhibition of endogenous KLK6[1]. DKFZ-251 (2.5-10 μM; 30 min) specifically inhibits the labeling of recombinant KLK6 by the activity-based probe DKFZ-633[1].
References:
[1]. De Vita E, et al. Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity. J Med Chem. 2018;61(19):8859-8874.
In Vitro, DKFZ-251 (compound 11) (200 μM; 1 h) forms a long-lived acyl-enzyme complex with recombinant triple-mutant KLK6, with a half-life of 6.43 h[1]. DKFZ-251 (100-500 nM; 48 h) induces a dose-dependent increase in BrdU incorporation and causes phenotypic changes in FaDu cells, which is consistent with the targeted inhibition of endogenous KLK6[1]. DKFZ-251 (2.5-10 μM; 30 min) specifically inhibits the labeling of recombinant KLK6 by the activity-based probe DKFZ-633[1].
References:
[1]. De Vita E, et al. Depsipeptides Featuring a Neutral P1 Are Potent Inhibitors of Kallikrein-Related Peptidase 6 with On-Target Cellular Activity. J Med Chem. 2018;61(19):8859-8874.