Solution formulation development and efficacy of MJC13 in a preclinical model of castration-resistant prostate cancer

Abstract

MJC13, a novel FKBP52 targeting agent, has potential use for the treatment of castration-resistant prostate cancer. The purpose of this work was to develop a solution formulation of MJC13, and obtain its efficacy profile in a human prostate cancer xenograft mouse model. Preformulation studies were conducted to evaluate the physicochemical properties. Co-solvent systems were evaluated for aqueous solubility and tolerance. A human prostate cancer xenograft mouse model was established by growing 22Rv1 prostate cancer cells in C.B-17 SCID mice. The optimal formulation was used to study the efficacy of MJC13 in this preclinical model of castrate-resistant prostate cancer. We found that MJC13 was stable (at least for 1 month), highly lipophilic (logP = 6.49), poorly soluble in water (0.28 µg/mL), and highly plasma protein bound (>98%). The optimal formulation consisting of PEG 400 and Tween 80 (1:1, v/v) allowed us to achieve a MJC13 concentration of 7.5 mg/mL, and tolerated an aqueous environment. After twice weekly intratumoral injection with 10 mg/kg MJC13 in this formulation for four consecutive weeks, tumor volumes were significantly reduced compared to vehicle-treated controls.

• Androgen-independent
• castration-resistant prostate cancer
• efficacy
• formulation
• MJC13
• preformulation

Declaration of interest

The authors report no declarations of interest.

HX has research grant support from an NIH/RTRN grant (5U54RR022762-05), NIH/NIGMS grant (1SC3GM102018-01) and from NIH/NIMHD/RCMI grant (2G12MD007605-22A1). MBC has research grant support from NIH/NCRR/RCMI grant (5G12RR008124), NIH/NIMHD/RCMI grant (G12MD007592), NIH/NIGMS grant (SC1GM084863) and State of Texas CPRIT grant (RP110444-P2).