TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

McCoy, Melissa K; Tansey, Malú G

doi:10.1186/1742-2094-5-45

Journal of Neuroinflammation

Table 1 Selected TNF inhibitors.

From: TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease

Inhibitor (Trade name)	Class	Description/Mode of Action	Specificity	Developer and Stage	References
Adalimumab (Humira)	Monoclonal antibody	Humanized bivalent mouse IgG1 monoclonal antibody; binds to ligands	solTNF, tmTNF	Abbott FDA approved 2005	[100–103, 179, 180]
Apratastat	Small molecule	Dual TACE and MMP inhibitor	MMPs, TACE	Wyeth Phase II terminated 2006	[121]
BMS-561392	Small molecule	Specific TACE inhibitor	TACE	Bristol-Myers Squibb Phase II	[121]
Certolizumab (Cimzia)	Monoclonal antibody	PEGylated antibody fragment	solTNF, tmTNF	UCB FDA approved 2008	[182]
CYT007-TNFQb	Vaccine	Anti-TNF vaccine	TNF	Cytos Biotechnology Phase I-IIa	[181]
DN-TNF (XPro1595)	Inactive TNF variant	TNF monomers engineered with point mutations to disrupt binding to TNFRs; exchange with solTNF to form dominant-negative heterotrimers; tmTNF-sparing	solTNF	Xencor Preclinical	[105, 106]
ESBA105	Antibody fragment	Single-chain antibody fragment directed against TNF	TNF	Esbatech (Zurich) Preclinical	[181]
Etanercept (Enbrel)	Receptor biologic	Human IgG fused to a dimer of the extracellular regions of TNFR2; binds to ligands	solTNF, tmTNF, Lympotoxin A	Amgen; Wyeth; Takeda FDA approved 1998	[179, 180]
Golimumab (CNTO148)	Monoclonal antibody	Human monoclonal antibody; binds to ligands	solTNF, tmTNF	Centocor, Schering-Plough Phase III	[101]
GW333	Small molecule	Dual TACE and MMP inhibitor	MMPs, TACE	GlaxoSmithKline Preclinical	[121]
Infliximab (Remicade)	Monoclonal antibody	Murine-human Chimeric bivalent IgG1 monoclonal antibody; binds to ligands	solTNF, tmTNF	Centocor Schering-Plough FDA approved 1998	[179, 180]
Lenercept	Receptor biologic	Dimeric TNFR1 receptor extracellular domain fused to a human IgG1heavy chain fragment; binds to ligands	solTNF, tmTNF, Lympotoxin A	Roche Phase III terminated	[101, 131, 183]
Minocycline	Small molecule	Broad-spectrum tetracycline antibiotic; inhibits synthesis of TNF and other inflammatory mediators	solTNF, tmTNF, MMPs, COX-2, prostaglandin E2	Off patent	[110–117]
tgAAC94	Gene therapy	AAV vectors containing the TNFR2:Fc fusion	solTNF, tmTNF, Lympotoxin A	Targeted Genetics Phase I-II	[184]
Thalidomide	Small molecule	Immunomodulatory drug; increases degradation of mRNA of a number of inflammatory genes	TNF, COX-2, IL-1β, TGF-β, IL-12 and IL-6.	Celgene Corporation FDA approved 1998	[118, 119]

Abbreviations: solTNF, soluble tumor necrosis factor; tmTNF, transmembrane tumor necrosis factor; TACE, tumor necrosis factor alpha converting enzyme; MMP, matrix metalloprotease; DN-TNF, dominant-negative tumor necrosis factor; TNFR, tumor necrosis factor receptor; COX-2, cyclo-oxygenase-2; IL1-β, interleukin-1beta; TGF-β, transforming growth factor beta; IL-12, interleukin-12; IL-6, interleukin-6.

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ISSN: 1742-2094

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