(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Hemangioma--Cavernous--Central-Nervous-System

Cerebral cavernous malformations (CCMs) are common vascular anomalies that develop in the central nervous system and, more rarely, the retina. The lesions can cause headache, seizures, focal neurological deficits, and hemorrhagic stroke. Symptomatic lesions are treated according to their presentation; however, targeted pharmacological therapies that improve the outcome of CCM disease are currently lacking. We performed a high-throughput screen to identify Food and Drug Administration-approved drugs or other bioactive compounds that could effectively suppress hyperproliferation of mouse brain primary astrocytes deficient for CCM3. We demonstrate that fluvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase and the

Topics: Animals; Astrocytes; Diphosphonates; Drosophila; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endothelial Cells; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hemangioma, Cavernous, Central Nervous System; High-Throughput Screening Assays; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Imidazoles; Indoles; Male; MAP Kinase Signaling System; Mice; Pregnancy; Protein Prenylation; Zoledronic Acid