K-858 is a small molecule inhibitor of Eg5 (kinesin spindle protein), a mitotic kinesin that plays an essential role in establishing mitotic spindle bipolarity. K-858 blocked centrosome separation, activated the spindle checkpoint, and induced mitotic arrest in cells accompanied by the formation of monopolar spindles. K858 induces mitotic arrest, apoptosis, and cell growth inhibition in cancer cells. K-858 exhibited potent antitumor activity in xenograft models of cancer, and induced the accumulation of mitotic cells with monopolar spindles in tumor tissues.

BVT-2733 is an inhibitor of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) that exhibits anti-diabetic, anti-inflammatory, and anti-osteoporotic properties. BVT-2733 decreases blood glucose and serum insulin levels in animal models of hyperglycemia. BVT-2733 also attenuates arthritis severity, decreases pro-inflammatory cytokine production, and suppresses synovial inflammation. In other animal models, this compound prevents 11βHSD-induced osteogenic differentiation and suppression of osteogenesis. BVT-2733 had reasonable mouse potency (IC50 = 96nM) but was only weakly active against the human isoform (IC50 = 3341 nM). This combined with moderate mouse pharmacokinetics (F = 21%) made it a suitable in vivo tool with which to explore the potential of 11β-HSD1 as a mechanism for the treatment of type II diabetes. In KKAy mice, oral dosing twice daily (25, 50, 100 mg/kg) of BVT-2733 lowered blood glucose levels in a dose-dependent manner.