CI-959 (free acid)

CI-959 free acid is an orally active cell activation inhibitor. CI-959 free acid selectively suppresses inflammatory cell activation post-receptor signaling via inhibiting calcium influx and weak calmodulin antagonism, without targeting PLC, PKC or NADPH oxidase. CI-959 free acid blocks lung allergic mediator release, anti-IgE bronchial contraction, neutrophil function, T-cell proliferation and DC marker expression while sparing monocytes. CI-959 free acid provides gastric cytoprotection by inhibiting leukocyte adhesion and suppresses tumor motility through F-actin reduction. CI-959 free acid can be used for research on allergies, inflammation, autoimmune diseases, gastric injury, and tumor metastasis ^{[1][2][3][4][5][6][7][8]}. In Vitro:CI-959 (0.1-100 μM) free acid inhibits spontaneous neutrophil migration and fMLP-induced chemotaxis in human peripheral blood neutrophils, with IC₅₀ values of 3.6 and 3.1 μM, respectively^[3].
CI-959 (100 μM) free acid shows no significant inhibition of fMLP receptor binding in human peripheral blood neutrophils, but only mildly inhibits phagocytosis of opsonized yeast^[3].
CI-959 (0.1-100 μM) free acid selectively inhibits respiratory burst induced by stimuli that promote calcium mobilization or calcium influx in human peripheral blood neutrophils, but does not act on NADPH oxidase itself and does not have oxygen free radical scavenging activity^[3].
CI-959 (0.1-100 μM) free acid selectively suppresses primary granule degranulation, with negligible activity against secondary granule secretion and PKC-dependent degranulation; it has no direct enzyme inhibition or cytotoxicity in human peripheral blood neutrophils^[3].
CI-959 free acid acts upstream of arachidonic acid metabolism via calcium signaling, without direct inhibition of 5-LO or COX enzymes in human peripheral blood neutrophils^[3].
CI-959 (100 μM) free acid targets downstream of PLC and IP3 receptor, blunts neutrophil calcium signaling by inhibiting extracellular Ca²⁺[3].
CI-959 (5-10 μM) free acid directly blocks inflammatory mediator-induced leukocyte-endothelial adhesion without disturbing microcirculatory hemodynamics^[4].
CI-959 (0.0075-75 μM; 10 min) free acid potently inhibits immunologically induced mediator release from human and guinea pig lung in vitro, with marked suppression of histamine and leukotriene release^[5].
CI-959 (1-10 μM; 10 min) free acid almost completely inhibits anti-IgE-induced human bronchial smooth muscle contraction^[5].
CI-959 (0.3-100 μM; 24 h) free acid concentration-dependently inhibits Con A (Concanavalin A (Biotinylated)) (HY-NP0174)-stimulated IL-2 release in rat spleen cells and human lymphocytess^[6].
CI-959 (0.03-300 μM) free acid potently suppresses ConA-triggered proliferation (IC₅₀=4.7 μM for rat splenocytes, 5.4 μM for human lymphocytes) and MLR responses (IC₅₀=3.5 μM), and this ConA inhibitory effect cannot be rescued by exogenous IL-2s^[6].
CI-959 (0.01-100 μM) free acid rapidly and in a concentration-dependent manner inhibits the spontaneous polarity of Walker carcinosarcoma cells, and this effect is reversible^[7].
CI-959 (10 μM; 30 min) free acid almost completely inhibits the spontaneous motility of Walker carcinosarcoma cells^[7].
CI-959 (0.001-100 μM) free acid concentration-dependently reduces F-actin content in Walker carcinosarcoma cells, closely correlating with inhibition of cell polarity^[7].
CI-959 (0.01-30 μM; 30 min) free acid inhibition of Walker cell polarity is independent of extracellular calcium^[7].
CI-959 (30 μM) free acid only induces minor shifts of intracellular calcium, and its anti-motile function persists under low-calcium conditions, ruling calcium signaling as its primary mechanism^[7].
CI-959 (1-100 μM; 24-72 h) free acid has no direct hypertrophic effect on cardiomyocytes; cardiac hypertrophy is not a direct compound effect^[8].
CI-959 (0.67 nM-6.7 μM; 30 min) free acid has minimal direct β-adrenoceptor binding activity, ruling out direct catecholaminergic effects^[8].
In Vivo:CI-959 (0.5-60 mg/mL; intranasal instillation; once daily; for 14 days) free acid exhibits local toxicity to the respiratory and olfactory epithelium of the rat nasal cavity, with the olfactory epithelium being more sensitive than the respiratory epithelium^[1].
CI-959 (10-90 mg/mL; intranasal instillation; once daily; for 14 days) free acid has local toxicity to the respiratory epithelium of the canine nasal cavity^[1].
CI-959 free acid (25-75 mg/kg; p.o.; once daily; for 14 days) exhibits no significant immunotoxicity in rats at doses that do not alter body weight or organ weights^[2].
CI-959 (25-75 mg/kg; p.o.; once daily; for 14 days) free acid does not impair the host resistance of mice to bacteria and tumors^[2].
CI-959 (0.0001-100 mg/kg; p.o.; single dose) free acid exhibits potent cytoprotective activity against NSAID (Aspirin (HY-14654), Indomethacin (HY-14397)) and ethanol-induced gastric mucosal damage in Sprague-Dawley rat, with ED₅₀ values of 0.05 mg/kg (aspirin), 1.0 mg/kg (indomethacin), and 0.07 mg/kg (ethanol), respectively^[4].
CI-959 (5 mg/kg; p.o.; single dose) free acid prophylactic administration reduces the severity of gastric damage but does not accelerate the healing process after injury in Sprague-Dawley rat^[4].
CI-959 (5 mg/kg; p.o.; once daily) free acid has no significant effect on the healing rate of gastric injuries induced by ethanol or indomethacin in Sprague-Dawley rat^[4].
CI-959 (50-200 mg/kg; p.o.; single dose) free acid does not inhibit gastric acid secretion in a rat basal gastric acid secretion model^[4].
CI-959 (0.1-10 mg/kg; p.o.; single dose) free acid dose not inhibit gastric acid secretion in a Beagle dog model of stimulated gastric acid secretion^[4].
CI-959 (2-50 mg/kg; p.o.; single dose) free acid’s protective effect on gastric cells does not involve the inhibition of the arachidonic acid metabolic pathway in Sprague-Dawley rat^[4].
CI-959 (0.1-100 mg/kg; p.o.; single dose) free acid does not exert cytoprotective effects via regulating intracellular sulfhydryl levels in Sprague-Dawley rat^[4].
CI-959 (1-10 mg/kg; p.o.; single dose) free acid effectively inhibits indomethacin-induced leukocyte adhesion in Sprague-Dawley rat^[4].
CI-959 (25 mg/kg; i.v.; single dose) free acid exhibits gastric cytoprotection after intravenous administration in Sprague-Dawley rat, indicating that its protective effect is independent of local gastrointestinal effects^[4].
CI-959 (3-30 mg/kg; i.v.; once daily; for 14 days) free acid induces reversible cardiac hypertrophy in male Wistar rats, with no myocardial injury or CPK/LDH isozyme changes^[8].
CI-959 (30-100 mg/kg; i.v.; once daily; for 10.5 days) free acid fails to induce cardiac hypertrophy without high plasma drug peaks in Male Wistar rats, confirming Cmax as the critical toxic determinant^[8].
CI-959 (25 mg/kg; i.v.; once daily; for 10 days) free acid-associated cardiac hypertrophy is mediated by endogenous catecholaminergic stimulation of cardiac β₁-adrenoceptors in Male Wistar rats^[8].
CI-959 (100 mg/kg; p.o.; once daily; for 7 days) free acid only triggers mild transient hypotension and slight brief catecholamine elevation in Male Wistar rats, while dopamine levels stay constant^[8].
CI-959 (25 mg/kg; i.v.; once daily; for 7 days) free acid induces persistent hypotension and marked rises in plasma epinephrine and norepinephrine without compensatory tachycardia in Male Wistar rats^[8].