title: Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein.
abstract: Our previous studies have demonstrated that expression of epidermal fatty acid binding protein (E-FABP) in tumor associated macrophages (TAMs) promotes macrophage anti-tumor activity by enhancing IFNβ responses in tumor models. Thus, E-FABP represents a new protective factor in enhancing tumor immune surveillance against tumor development. Herein, we report the compound 5-(benzylamino)-2-(3-methylphenyl)-1,3-oxazole-4-carbonitrile (designated EI-05) as a novel E-FABP activator for inhibition of mammary tumor growth. EI-05 was selected from the ZINC compound library using molecular docking analysis based on the crystal structure of E-FABP. Although EI-05 is unable to bind E-FABP directly, it significantly increases E-FABP expression in macrophages during inflammation. Stimulation of macrophages with EI-05 remarkably enhances lipid droplet formation and IFNβ production, which further promotes the anti-tumor activity of macrophages. Importantly, administering EI-05 in vivo significantly inhibits mammary tumor growth in a syngeneic mouse model. Altogether, these results suggest that EI-05 may represent a promising drug candidate for anti-tumor treatment through enhancing E-FABP activity and IFNβ responses in macrophages.
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Enyu
authors: E
authors: Rao
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Puja
authors: P
authors: Singh
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Xiuhong
authors: X
authors: Zhai
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Yan
authors: Y
authors: Li
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Ganqian
authors: G
authors: Zhu
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Yuwen
authors: Y
authors: Zhang
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Jiaqing
authors: J
authors: Hao
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Young-In
authors: YI
authors: Chi
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Rhoderick E
authors: RE
authors: Brown
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Margot P
authors: MP
authors: Cleary
authors: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors: Bing
authors: B
authors: Li
mesh_terms: D000818:Animals; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D016899:Interferon-beta / Q000096:biosynthesis / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology*; D010080:Oxazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C493412:FABP5 protein, human; D050556:Fatty Acid-Binding Proteins; D009570:Nitriles; D010080:Oxazoles; D016899:Interferon-beta
keywords: E-FABP; interferon β; tumor associated macrophages; tumor treatment