{Reference Type}: Journal Article
{Title}: Preclinical evaluation of ELP-004 in mice.
{Author}: McCall JL;Geldenhuys WJ;Robinson LJ;Witt MR;Gannett PM;Söderberg BCG;Blair HC;Soboloff J;Barnett JB;
{Journal}: Pharmacol Res Perspect
{Volume}: 12
{Issue}: 4
{Year}: 2024 Aug
{Factor}: 2.963
{DOI}: 10.1002/prp2.1230
{Abstract}: This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP-004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease-modifying antirheumatic drugs, are not well-tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP-004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP-004 was non-mutagenic, did not induce chromosome aberrations, non-cardiotoxic, and had minimal off-target effects. Using in vitro hepatic systems, we found that ELP-004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP-004 inhibits osteoclast differentiation without suppressing overall T-cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice.