CB-5083 is a novel first in class, potent orally bio-available p97 inhibitor that disrupts cellular protein homeostasis and demonstrates anti-tumor activity in solid and hematological models. CB-5083 causes rapid and sustained accumulation of poly-ubiquitin in tumor xenografts after a single administration. CB-5083 showed activity to inhibit tumor growth in multiple rodent models of human cancer. Furthermore, CB-5083 appears to exhibit greater potency over current proteasome inhibitors that further validate targeting p97 and protein homeostasis in the treatment of cancer. CB-5083 is a potent inhibitor of endoplasmic reticulum associated degradation and induces a lethal unfodled protein response. CB-5083 recently began Phase 1 testing in relapsed/refractory or refractory multiple myeloma, and advanced solid tumors.

Vesnarinone is a new and novel inotropic drug that has unique and complex mechanisms of action. It inhibits phosphodiesterase, thereby leading to increased intracellular calcium, and also affects numerous myocardial ion channels, resulting in the prolongation of the opening time of sodium channels and the decrease in the delayed outward and inward rectifying potassium current. In vitro, it has also demonstrated significant effects on cytokine production, which may account for some of its observed clinical benefits. Hemodynamic studies in humans with congestive heart failure reveal that vesnarinone can improve ventricular function. Placebo-controlled studies in large numbers of patients with heart failure have suggested a morbidity and mortality benefit with a 60 mg daily dose. In Japan, vesnarinone was approved in June 1990 and first marketed in September 1990.