Support for phosphoinositol 3 kinase and mTOR inhibitors as treatment for lupus using in-silico drug-repurposing analysis

Table 1 Drugs obtained and their biological targets

Score^a	Biological target	Action	Drugs	p value
+	Topoisomerase II	Inhibitor	Amsacrine, amonafide, teniposide, etoposide, idarubicin	2.829 × 10^–4
+	HDAC	Inhibitor	Panobinostat, scriptaid, dacinostat, vorinostat, trichostatin A	1.451 × 10^–4
+	Protein kinase C delta	Activator	Phorbol-12-myristate-13-acetate, ingenol	3.172 × 10^–3
+	Histone lysine methyltransferase	Inhibitor	Chaetocin
+	ARFGAP1	Inhibitor	QS11
+	PDK1	Inhibitor	BX795
+	Retinoic acid receptor beta	Inhibitor	Le135
+	Arginase	Inhibitor	Inhibitor Bec
+	JAK2/STAT3	Inhibitor	Cucurbitacin I
+	Fatty acid synthetase	Inhibitor	Cerulenin
+	Src, Bcr-Abl tyrosine kinase	Inhibitor	AG957
+	PLD2	Inhibitor	CAY10594
+	IKKβ	Inhibitor	Parthenolide
+	IMPDH1	Inhibitor	Mycophenolic acid
+	FTL3	Inhibitor	Midostaurin
+	DNA	Crosslinker	Mitomycin C
+	Tubulin	Inhibitor	Vinblastine
+	Hsp90	Inhibitor	Radicol
+	Multiple targets	Inhibitor	Resveratrol
–	PI3K	Inhibitor	PI828, GDC0941, NVP-BEZ235,PP110, TGX115	4.915 × 10^–6
–	mTOR	Inhibitor	NVP-BEZ235, AZD8055, TGX115, Ku0063794	1.792 × 10^–5
–	CDK	Inhibitor	BML259, indirubin	1.463 × 10^–2
–	IKBalfa	Inhibitor	Evodiamine
–	Farnesyltransferase	Inhibitor	Tipifarnib
–	IGF1R	Inhibitor	Linsitinib
–	MAP2K1	Inhibitor	Selumetinib
–	CHK1	Inhibitor	SB218078
–	Piruvate kinase	Inhibitor	M2PK activator
–	Rho kinase	Inhibitor	Rho kinase inhibitor III
–	Voltage-dependent calcium channel	Inhibitor	Nifedipine
–	Braf	Inhibitor	Vemurafenib

Table presents significant drugs with their biological target and their mechanism of action. p value calculated for groups of drugs with the same target using Fisher’s exact test
CDK cyclin-dependent kinase, HDAC histone deacetylase, mTOR mammalian target of rapamycin, PI3K phosphoinositol 3 kinase
^a + drugs with positive similarity score, – drugs with negative similarity score in regard to SLE signatures

ISSN: 1478-6362