(±) -CPSI 1306 is an inhibitor of macrophage inhibitory factor (MIF) [1].
MIF is a proinflammatory cytokine and is an important regulation element of innate immunity. MIF plays an important role in the pathogenesis of many autoimmune inflammatory diseases [1].
In Skh-1 hairless mice with UVB exposure, CPSI 1306 reduced myeloperoxidase (MPO) activity and skin thickness and increased p53 expression and keratinocyte apoptosis. In mice with squamous carcinogenesis, CPSI-1306 slowed tumor growth and reduced p53 foci in non-tumor skin [1]. In ICR mice with streptozotocin (STZ) -induced non-insulin-dependent diabetes mellitus (NIDDM), CPSI 1306 significantly decreased blood glucose levels and reduced the levels of IL-6 and TNF-ɑ, the proinflammatory cytokines. These results suggested that MIF was involved in the pathogenesis of NIDDM [2]. In wild-type C57Bl/6 mice immunized with myelin oligodendrocyte glycoprotein (MOG35–55), which induced experimental autoimmune encephalomyelitis (EAE), CPSI-1306 (1 mg/kg) reduced the inflammation and reduced the severity of disease [3].
References:
[1]. Nagarajan P, Tober KL, Riggenbach JA, et al. MIF antagonist (CPSI-1306) protects against UVB-induced squamous cell carcinoma. Mol Cancer Res, 2014, 12(9): 1292-1302.
[2]. Sanchez-Zamora Y, Terrazas LI, Vilches-Flores A, et al. Macrophage migration inhibitory factor is a therapeutic target in treatment of non-insulin-dependent diabetes mellitus. FASEB J, 2010, 24(7): 2583-2590.
[3]. Kithcart AP, Cox GM, Sielecki T, et al. A small-molecule inhibitor of macrophage migration inhibitory factor for the treatment of inflammatory disease. FASEB J, 2010, 24(11): 4459-4466.