Adherent cell assay results affected by variable z-position mixing.

We demonstrate that modifying mixing dynamics after addition of organic solute into aqueous buffers dramatically affects cell morphology and protein expression. Variable z-position (VZP) or varying the height of aspiration and dispense positions during mixing eliminates artifactual effects. Here, we tested 4 adherent cell types and show effects of VZP on quantitative imaging, protein expression, viability, and morphology.

(4-Piperidinylphenyl)aminoethyl amides as a novel class of non-covalent cathepsin K inhibitors.

A series of (4-piperidinylphenyl)aminoethyl amides based on dipeptide anilines were synthesized and tested against cathepsin K, cathepsin L and cathepsin B. These new non-covalent inhibitors exhibited single-digit nM inhibition of the cysteine proteases. Compounds 3 and 7 demonstrated potency in both mouse and human osteoclast resorption assays.