It is essential to determine the extent of protein binding of a therapeutic agent when considering the pharmacokinetic profile of a compound since plasma protein binding may greatly influence disposition and efficacy of a drug. The main purpose of this study was to investigate the protein binding abilities of a novel anti-cancer drug, ON 013105, which is currently entering clinical trials. This drug was harvested to target Mantle Cell Lymphoma (MCL) a rare, but deadly non-Hodgkin type lymphoma that accounts for about 10% of the malignant lymphomas.

The ultrafiltration method was employed to assess protein binding of the compound. Non-specific binding experiments were initially performed which deemed the method as suitable for providing accurate measurements of free drug concentration and binding capacity. Binding at five concentrations were considered: 10, 12.5, 25, 50 and 100 μg/ml across the mouse, rat, dog, monkey, and human species plasmas. The extent of protein binding was determined by quantitating the unbound fractions and total concentrations of ON 013105 using an HPLC method.

The results show that ON 013105 is a highly protein bound drug across the mouse, rat, dog, monkey and human plasmas at respective average percent bound values of 93.37, 98.51, >99, 97.15, and >99%. The percent bound values were consistent along the range of concentrations. This provides valuable information that may be crucial in evaluating the distribution of ON 013105 to MCL patients. Even though there are drugs in place to treat MCL, there remains a need for novel effective agents since the disease continues to express an overall survival rate of 3 to 5 years.