Table 1.
CaMKII inhibitors and related compounds.
| Inhibitor type | Controls/verification | Action of inhibitor |
|---|---|---|
| KN-93/KN-62 | KN-92; GFP-AC3-I transgene | KN-93 blocked pacing induced atrial fibrillation in the Ryr2 R176Q/+ mouse model (Chelu etal., 2009). |
| KN-92; AIP; CaMKIIδ knockout | KN-93, AIP, and knockout block cardiac arrhythmogenesis and sarcoplasmic reticulum Ca2+ leak (Sag etal., 2009). | |
| KN-92 | KN-93 and AIP were used to demonstrate that CaMKII is linked to SAN cell bioenergetics, affecting both ATP consumption and ATP generation (Yaniv etal., 2013). | |
| KN-92; CaMKIIδ knockout | KN-93 blocks increase in GlcNAcylation-dependent Ca2+ spark frequency and prevents premature ventricular complexes also seen in diabetes (Erickson etal., 2013). | |
| AC3-I/AIP | GFP-AC3-C | Myocardial GFP-AC3-I transgene blocked maladaptive remodeling following chronic β-adrenergic stimulation or myocardial infarct with GFP-AC3-I (Zhang etal., 2005). |
| GFP-AC3-C;KN-93/KN-92 | Myocardial GFP-AC3-I transgene in calcineurin hypertrophy model primarily reduced ventricular arrhythmias, improved mechanical function, and decreased mortality with minimal effect on the hypertrophic phenotype (Khoo etal., 2006). | |
| GFP-AC3-C | AngII promoted AF was blocked by GFP-AC3-I and prevented by knockins with oxidation resistant CaMKII(MM > VV) or RyR2 lacking CaMKII phosphorylation site (RyR2S2814A; Purohit etal., 2013). | |
| GFP-AC3C; CaMKIIN | Myocardial GFP-AC3-I and blocked increase mortality of diabetic mice after myocardial infarction via reactive oxygen species and confirmed with CaMKII(MM > VV) mice (Luo etal., 2013). | |
| CaMKIIN | Myocardial GFP-AC3-I and -AC3-C | GFP-CaMKIIN (sinoatrial node expressed) blocked isoproterenol-stimulated CaMKII activation and reduced the fight or flight heart rate response to stress or isoproterenol (Wu etal., 2009). |
| GFP; AC3-I | GFP-CaMKIIN (sinoatrial node expressed) blocked AngII and ROS activation of CaMKII and cell death contributing to sinus node dysfunction (Swaminathan etal., 2011). | |
| AC3-I; shRNA; KN-93 | HA-CaMKIIN targeted to cytoplasmic membranes acts outside the nucleus to mediate induction of complement factor B following myocardial infarct (Singh etal., 2009). | |
| CaMKII (Thr287Asp) | mtCaMKIIN (with mitochondrial localization sequence) and palmitoyl-CaMKIIN for membrane localization support a role of mitochondrial CaMKII in ischemia reperfusion injury, MI and neurohumoral injury due to increased inner membrane mitochondrial Ca2+ uniporter current (Joiner etal., 2012). |