WEB 2086 (Apafant) is a water-soluble, selective, and potent platelet-activating factor (PAF) antagonist, with a Ki value of 9.9nM[1]. By targeting PAF, WEB 2086 reduces thromboxane B2, leukotriene C4, and histamine levels and prevents increases in microvascular permeability[2]. WEB 2086 has been widely used in animal models of asthma to restrain microvascular leakage and excessive mucus secretion[3].
In vitro, WEB 2086 treatment for 72 hours significantly suppressed the proliferation of MCF-7, MDA-MB-231, and HT-1080 cells, with IC50 values of 650µM, 410µM, and 380µM, respectively[4]. Incubation with 1mM WEB 2086 for 3 days induced apoptosis in NB4 cells, accompanied by extensive nuclear fragmentation, DNA fragmentation, and caspase-3 activation[5]. 1mM of WEB 2086 incubation for 5 days reduced the growth and hemoglobin accumulation of murine erythroleukemia cells (MELCs), enhanced the expression of globin genes, and downregulated the expression of c-Myb[6].
In vivo, daily intraperitoneal injection of WEB 2086 at a dose of 5mg/kg for 10 days alleviated laser-induced choroidal neovascularization (CNV) in mice, decreased the infiltration of macrophages in the retinal pigment epithelium-choroid complex[7]. One hour before antigen challenge, an oral administration of WEB 2086 (100mg/kg) markedly mitigated the airway response in guinea pigs[8].
References:[1] Kato M, Imoto K, Miyake H, et al. Apafant, a potent platelet-activating factor antagonist, blocks eosinophil activation and is effective in the chronic phase of experimental allergic conjunctivitis in guinea pigs[J]. Journal of pharmacological sciences, 2004, 95(4): 435-442.
[2] Akagi M, Nishioka E, Kanoh R, et al. Inhibitor effect of apafant on bronchopulmonary responses to platelet activating factor and to antigen in rats[J]. Arzneimittel-forschung, 1997, 47(12): 1364-1369.
[3] Tamura G, Takishima T, Mue S, et al. Effect of a potent platelet-activating factor antagonist, WEB-2086, on asthma: a multicenter, double-blind placebo-controlled study in Japan[M]//Platelet-Activating Factor and Related Lipid Mediators 2: Roles in Health and Disease. Boston, MA: Springer US, 1996: 371-380.
[4] Cellai C, Laurenzana A, Vannucchi A M, et al. Growth inhibition and differentiation of human breast cancer cells by the PAFR antagonist WEB-2086[J]. British Journal of Cancer, 2006, 94(11): 1637-1642.
[5] Laurenzana A, Cellai C, Vannucchi A M, et al. WEB-2086 and WEB-2170 trigger apoptosis in both ATRA-sensitive and-resistant promyelocytic leukemia cells and greatly enhance ATRA differentiation potential[J]. Leukemia, 2005, 19(3): 390-395.
[6] Cellai C, Laurenzana A, Vannucchi A M, et al. Specific PAF antagonist WEB‐2086 induces terminal differentiation of murine and human leukemia cells[J]. The FASEB Journal, 2002, 16(7): 733-735.
[7] Zhang H, Yang Y, Takeda A, et al. A novel platelet-activating factor receptor antagonist inhibits choroidal neovascularization and subretinal fibrosis[J]. PloS one, 2013, 8(6): e68173.
[8] Ikegami K, Hata H, Fuchigami J, et al. Apafant (a PAF receptor antagonist) suppresses the early and late airway responses in guinea pigs: a comparison with antiasthmatic drugs[J]. European journal of pharmacology, 1997, 328(1): 75-81.