PMID- 25796556
OWN - NLM
STAT- MEDLINE
DCOM- 20160526
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 6
IP  - 10
DP  - 2015 Apr 10
TI  - Inhibition of tumor growth by a newly-identified activator for epidermal fatty 
      acid binding protein.
PG  - 7815-27
AB  - 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 IFNbeta 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 IFNbeta 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 IFNbeta responses in 
      macrophages.
FAU - Rao, Enyu
AU  - Rao E
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Singh, Puja
AU  - Singh P
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Zhai, Xiuhong
AU  - Zhai X
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Li, Yan
AU  - Li Y
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Zhu, Ganqian
AU  - Zhu G
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Zhang, Yuwen
AU  - Zhang Y
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Hao, Jiaqing
AU  - Hao J
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Chi, Young-In
AU  - Chi YI
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Brown, Rhoderick E
AU  - Brown RE
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Cleary, Margot P
AU  - Cleary MP
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
FAU - Li, Bing
AU  - Li B
AD  - The Hormel Institute, University of Minnesota, Austin, MN, USA.
LA  - eng
GR  - R01 HL125353/HL/NHLBI NIH HHS/United States
GR  - R01 CA157012/CA/NCI NIH HHS/United States
GR  - R01 CA177679/CA/NCI NIH HHS/United States
GR  - R01 GM045928/GM/NIGMS NIH HHS/United States
GR  - R01 GM45928/GM/NIGMS NIH HHS/United States
GR  - R01 CA180986/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (FABP5 protein, human)
RN  - 0 (Fatty Acid-Binding Proteins)
RN  - 0 (Nitriles)
RN  - 0 (Oxazoles)
RN  - 77238-31-4 (Interferon-beta)
SB  - IM
MH  - Animals
MH  - Fatty Acid-Binding Proteins/biosynthesis/*metabolism
MH  - Female
MH  - Humans
MH  - Interferon-beta/biosynthesis/metabolism
MH  - Macrophage Activation/drug effects
MH  - Macrophages/drug effects/metabolism
MH  - Mammary Neoplasms, Experimental/drug therapy/metabolism
MH  - Mice
MH  - Models, Molecular
MH  - Nitriles/chemistry/*pharmacology
MH  - Oxazoles/chemistry/*pharmacology
PMC - PMC4480718
OTO - NOTNLM
OT  - E-FABP
OT  - interferon beta
OT  - tumor associated macrophages
OT  - tumor treatment
COIS- CONFLICTS OF INTEREST The authors declare no conflict of interest.
EDAT- 2015/03/23 06:00
MHDA- 2016/05/27 06:00
PMCR- 2015/04/10
CRDT- 2015/03/23 06:00
PHST- 2015/11/20 00:00 [received]
PHST- 2015/02/04 00:00 [accepted]
PHST- 2015/03/23 06:00 [entrez]
PHST- 2015/03/23 06:00 [pubmed]
PHST- 2016/05/27 06:00 [medline]
PHST- 2015/04/10 00:00 [pmc-release]
AID - 3485 [pii]
AID - 10.18632/oncotarget.3485 [doi]
PST - ppublish
SO  - Oncotarget. 2015 Apr 10;6(10):7815-27. doi: 10.18632/oncotarget.3485.