Table 1. Candidate targets identified in RNAi B-cell activation screen sorted by availability of structural data.

The top ten candidate targets are suitable for structure-based drug repositioning screening. For 10 candidate targets (number 11 to 20) no structures were available and thus they could not be used for structure -based drug repositioning. Silencing of all listed candidate targets leads to strong the downregulation of CD70 and CD80 expressions in the B cell Namalwa cell line activated by the TLR9 agonist ODN2006 without causing cell death (column cell survival). A literature study links nearly all candidate targets to cancer (C) and some to autoimmune diseases (AD) or cancer of the immune system (CIS). Overall, there are many novel autoimmune candidate targets and KDR (VEGFR2) emerges as one very promising with 36 protein structures, potent decrease in expression of CD70 and CD80 following knock out of target in activated Namalwa cells without affecting cell viability and links to both cancer and auto-immunity.

	Gene name	Protein name	PDB structures	CD70 down regulation	CD80 down regulation	% Cell survival	C	CIS	AD
1	DAPK1	Death-associated protein kinase 1	39	1.21	0.87	100	x	x	x
2	KDR	Vascular endothelial growth factor receptor 2 (VEGFR2)	36	1.27	0.98	75.6	x	x	x
3	NEK2	Serine/threonine-protein kinase Nek2	24	1.37	0.79	100	x	x
4	CSNK1D	Casein kinase I isoform delta (CK1d)	17	0.97	1.28	100	x
5	EPHB4	Ephrin type-B receptor 4	14	1.95	0.74	100	x
6	CDC7	Cell division cycle 7-related protein kinase	4	1.88	0.83	100	x
7	ILK	Integrin-linked protein kinase	2	1.28	0.95	100	x
8	MST-4	Serine/threonine-protein kinase 26	2	2.63	0.73	100	x		x
9	MAP2K2	Dual specificity mitogen-activated protein kinase kinase 2	2	1.32	0.67	82.9	x
10	MLK4	Mitogen-activated protein kinase kinase kinase 21	1	1.81	0.54	99.7	x
11	PXK	PX domain-containing protein kinase-like protein	0	1.16	0.54	94.4			x
12	PTK7	Inactive tyrosine-protein kinase 7	0	1.07	0.71	86.2	x	x
13	PAK3	Serine/threonine-protein kinase PAK 3	0	2.83	0.98	86.8	x
14	BRSK1	Serine/threonine-protein kinase	0	1.76	0.83	100	x
15	FER	Tyrosine-protein kinase Fer	0	1.60	0.95	100	x
16	IRAK-3	Interleukin-1 receptor-associated kinase 3	0	1.70	1.02	93.3	x		x
17	MAP3K10	Mitogen-activated protein kinase kinase kinase 10	0	1.65	0.93	87.0	x
18	PRKAG2	5’-AMP-activated protein kinase subunit gamma-2	0	1.57	0.74	100	x
19	SCYL1	N-terminal kinase-like protein	0	1.18	0.68	84.6	x
20	STK33	Serine/threonine-protein kinase 33	0	1.43	0.92	100	x
21	TXK	Tyrosine-protein kinase TXK	0	1.49	1.06	79.9
22	WNK2	Serine/threonine-protein kinase WNK2	0	1.47	0.86	100	x