Mocravimod (hydrochloride)

Mocravimod (hydrochloride) is an orally active sphingosine-1-phosphate receptor (S1PR) modulator that blocks the signal required by T cells to egress from lymph nodes and other lymphoid organs. Mocravimod (hydrochloride) preferentially binds to S1PR1 over S1PR2 and S1PR3 in cardiomyocytes. Mocravimod (hydrochloride) significantly lowered the concentration of reactive oxygen species (ROS), prevented mitochondrial permeability transition pore opening, boosted mitochondrial membrane potential (MMP), and increased phosphorylation of AKT, EKR, GSK-3β, JAK2, and STAT3. Mocravimod (hydrochloride) retains T cell effector function. Mocravimod (hydrochloride) can be used for the study of acute myelogenous leukemia, diabetes and Myocardial Ischemia-Reperfusion Injury (MIRI)^[1][2][3][4]. IC50 & Target:S1PR1^[1] In Vitro:Mocravimod (KRP203) (0.2-5 μM, 24 h) (hydrochloride) significantly improves the survival rate of the hypoxia-reoxygenation (H/R) H9c2 cells, reduces lactate dehydrogenase (LDH) release, and decreases apoptosis^[4].
Mocravimod (0.2-1 μM, 24 h) (hydrochloride) significantly reduces reactive oxygen species (ROS) levels, improves mitochondrial membrane potential, and inhibits the opening of the mitochondrial permeability transition pore (mPTP) in hypoxia-reoxygenation (H/R) H9c2 cells^[4].
Mocravimod (0.2-1 μM, 24 h) (hydrochloride) inhibits the expression of mitochondrial-mediated apoptosis pathway proteins such as cytochrome C, caspase-9, and caspase-3^[4].
Mocravimod (0.2-1 μM, 24 h) (hydrochloride) significantly increases the phosphorylation levels of key signaling pathway proteins in hypoxia-reoxygenation (H/R) H9c2 cells, including AKT (Ser473), ERK (Thr202/Tyr204), GSK-3β (Ser9), JAK2 (Tyr1007/1008), and STAT3 (Ser727)^[4].
In Vivo:Mocravimod (KRP203) (once daily/twice daily, 1-5 days) (hydrochloride) significantly improves the survival rate of islet transplantation in C57BL/6 mice with diabetes induced by intravenous streptozotocin^[2].
Mocravimod (3.0 mg/kg, i.p., thrice weekly) (hydrochloride) significantly inhibits the development of atherosclerotic lesions in mice on a high-cholesterol diet, and this effect was independent of changes in blood lipids, but rather by regulating the infiltration of inflammatory cells within plaques^[3].