Target Validation Information
TTD ID	T32578
Target Name	Interleukin-6 (IL6)
Type of Target	Successful
Drug Potency against Target	C326	Drug Info	IC50 = 0.253 nM	[2]
Action against Disease Model	Tocilizumab	Drug Info	ELISA assay demonstrated that tociliz uMab bound to sIL-6R and inhibited IL-6 binding to sIL-6R in a dose-dependent manner. The dissociation constant (Kd value) for IL-6R was determined to be 2.54+/-0.12 nmol/L by Scatchard analysis. In addition, tociliz uMab had the ability to dissociate IL-6 and sIL-6R from their preformed complex. The immune complex of tociliz uMab and sIL-6R did not transmit signaling. Moreover, tociliz uMab suppressed the IL-6/sIL-6R complex-induced proliferation of h uMan gp130-transfected cell, BAF-h130. In addition, tociliz uMab had the ability to bind to h uMan IL-6R expressing COS-7 cells and to suppress the growth of the IL-6-dependent myeloma cell line. Tociliz uMab inhibited the proliferation of BaF/IL-6R induced by IL-6, but did not inhibit the proliferation of BaF/IL-11R, BaF/OSMR, BaF/LIFR and BaF/CNTFR cells induced by their corresponding cytokines. These lines of evidence indicate that tociliz uMab is able to bind to both sIL-6Rand mIL-6R and to inhibit IL-6 binding to its receptors, leading to the blockade of the IL-6 signaling through both sIL-6R and mIL-6R, but not block the signaling of other IL-6 family cytokines.	[1]
References
REF 1	Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family. Int Immunopharmacol. 2005 Nov;5(12):1731-40.
REF 2	Multivalent avimer proteins evolved by exon shuffling of a family of human receptor domains. Nat Biotechnol. 2005 Dec;23(12):1556-61.

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