Cyclocreatine

Cyclocreatine, a creatine analogue, acts as a brain-penetrant and potent bioenergetic protective agent by providing high levels of ATP. Cyclocreatine can be phosphorylated and dephosphorylated by creatine kinases. Cyclocreatine suppresses creatine metabolism ameliorating the cognitive, autistic and epileptic phenotype in a mouse model of creatine transporter defciency. Cyclocreatine protects against ischemic injury and enhances cardiac recovery during early reperfusion in dogs and rats. Cyclocreatine decreases plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Cyclocreatine is proming for research of ischemic heart disease, cardiovascular diseases, Alzheimer’s disease and other neurodegenerative diseases associated with microglial dysfunction, prostate cancer^{[1][2][3][4][5]}. In Vitro:Cyclocreatine (5 or 10 mM, 24 or 40 h) improves extracellular acidification rate (ECAR) which is accompanied by less Autophagy, increases mTOR signaling and cell viability in bone marrow-derived macrophages^[2].
Cyclocreatine (0-50 mM, 24 h) suppresses creatine metabolism, proliferation and creatine uptake in prostate cancer cells^[3].
In Vivo:Cyclocreatine (500 mg/kg, i.v., a single dose for 60 min) restores heart contractile function and shows markedly less myocardial cell injury when compared to the control (saline) group in the acute myocardial infarction (AMI) intact dog model^[1].
Cyclocreatine (0.28 mg/g, drink, supplementation daily from 10-week to 8 months) rescues microgliosis and clustering and moderates neurite dystrophy in TREM2^−/− 5XFAD mice^[2].
Cyclocreatine (40 mg, gavage, daily for 1 month) significantly reduces liver metastatic burden and affects prostate cancer progression in a model of liver metastasis of mice^[3].