Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Celiprolol is beta blocker, used to treat high blood pressure. Celiprolol is a selective β1 receptor antagonist, β2 receptor partial agonist. Celiprolol is not approved by the FDA, but is available worldwide under brand names Cardem, Selectol, Celipres, Celipro, Celol, Cordiax, Dilanorm. It is used to treat mild to moderate hypertension and angina prectoris. In 2010 celiprolol has demonstrated positive results in the prevention of vascular complications of Ehlers-Danlos syndrome. Celiprolol has fewer CNS-related side effects than other beta blockers presumably because of limited penetration through blood-brain barrier because of its solubility.