Table 1.
Drug class | Proposed mechanism of action | Name of drug (Company) | Current clinical research phase |
---|---|---|---|
Direct sarcomere activators | Directly activates myosin | Omecamtiv mercarbil (Cytokinetics) | Phase 3 |
Direct sarcomere activators | Directly activates myosin | MYK-491 (MyoKardia, Inc.) | Phase 1b/2a |
Phosphodiesterase inhibitors | Inhibits PDE9, augments cGMP | CRD-733 (Cardurion Pharmaceuticals) | Phase 1 |
Phosphodiesterase inhibitors | Inhibits PDE1, augments cGMP and cAMP | ITI-214 (Intracellular Therapies, Inc.) | Phase 1b/2a |
Nitroxyl donors | Antioxidant, enhances calcium sensitivity and calcium handling, augments NO signaling | BMS-986231 (Bristol-Myers Squibb) | Phase 2b |
Soluble guanylate cyclase stimulators | Augments cGMP-PKG signaling | Vericiguat (Bayer/Merck) | Phase 3 |
Apelin | Gαi activation and Inhibition of β-arrestin, ERK activation | CLR325 (Novartis); AMG986 (Amgen) | Phase 3; Phase 1 |
Anti-inflammatory agents | Blocks inflammatory interleukin 1β | Canakinumab (Novartis) | Phase 3 |
HFrEF, Heart failure with reduced ejection fraction; PDE, phosphodiesterase; cGMP, cyclic guanosine monophosphate; cAMP, cyclic adenosine monophosphate; NO, nitric oxide; PKG, Protein Kinase G; ERK, extracellular signal-regulated kinase