GDC-0834 Racemate is a novel, potent and selective BTK inhibitor with an in vitro IC50 of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC50 of 1.1 and 5.6 μM in mouse and rat, respectively. The development, differentiation, and proliferation of B-lineage cells depend on Bruton's tyrosine kinase (BTK), which makes it a desirable target for rheumatoid arthritis treatment. With IC(50) values of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and 1.1 and 5.6 μM in mouse and rat, respectively, in vivo, GDC-0834 suppressed BTK. GDC-0834 (30-100 mg/kg) was administered in a rat collagen-induced arthritis (CIA) model, and the reduction of morphologic pathology and ankle swelling occurred in a dose-dependent manner. Fitting ankle-diameter time-course data was an integrated pharmacokinetic/pharmacodynamic model of disease progression, where efficacy is driven by pBTK inhibition. In order to describe non-drug related reductions in ankle swelling that happen in CIA rats during later stages of the disease progression, this model included a transit model. The base model provided a good description of the time course of ankle swelling in vehicle animals. The data from the vehicle and GDC-0834-treated groups were fitted simultaneously, and the results indicated that a total of 73% inhibition of pBTK was required to cut in half the rate constant (k(in)) describing the increase in ankle swelling. These results imply that the pathway on inflammatory arthritis in rats requires a high level of pBTK inhibition for maximum activity.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.