CI-1018

CI-1018 is an orally active selective PDE-4 inhibitor, with IC₅₀ values of 1.1 μM, 35.8 μM, and 73.4 μM against hPDE-4, canine PDE-4, and guinea pig PDE-4, respectively. CI-1018 induces iNOS expression and Apoptosis. CI-1018 induces vascular injury, medial necrosis, hemorrhage, edema, thymic atrophy, ketonuria, and weight loss. CI-1018 can be used in research related to asthma, vasculitis, and mesenteric vasculitis/arteriopathy^[1][2][3][4]. In Vitro:CI-1018 inhibits PDE4 derived from U937 cells with an IC₅₀ of 1.1 μM, while it shows weak inhibitory effects on PDE3 derived from canine aorta and PDE1/PDE5 derived from guinea pig trachea^[3].
CI-1018 inhibits TNF-α release from peripheral blood mononuclear cells, with an IC₅₀ of 0.990 μM^[3].
CI-1018 inhibits the release of TNF-α in human whole blood (hWB) with an IC₅₀ of 61 μM^[3]. In Vivo:CI-1018 (750 mg/kg; p.o.; once daily; for 4 consecutive days) induces significant vasculitis in female Wistar rats, accompanied by characteristic urinary metabolomic changes that are directly associated with vascular injury rather than secondary inflammation^[1].
CI-1018 (administered orally, once 24 h and once 3 h prior to antigen challenge) inhibits antigen-induced airway eosinophil recruitment in sensitized Brown-Norway rats, with an oral ED₅₀ of 5.06 mg/kg^[3].
CI-1018 (10 mg/kg; p.o.) inhibits LPS-induced TNFα release by 25% in Wistar rats at an oral dose of 10 mg/kg^[3].
CI-1018 (750 mg/kg; p.o.; once daily; for 4 consecutive days) induces significant mesenteric vasculitis in female Wistar rats, accompanied by nitrative stress and medial smooth muscle cell apoptosis, whereas co-administration with Dexamethasone (HY-14648) abolishes the inflammatory response, markers of nitrative stress, and apoptotic phenomena^[4].
CI-1018 (750 mg/kg; p.o.; once daily; for 3 consecutive days) induces mesenteric vasculitis in female Wistar rats and mediates caspase-3 activation in their medial smooth muscle cells; neutrophil depletion reduces the severity of vasculitis but fails to eliminate caspase-3 immunoreactivity^[4].