The accumulation of abnormal prion protein (PrPSc) converted from the normal cellular isoform of PrP (PrPC) is assumed to induce pathogenesis in prion diseases. disorders 1 Conformational diseases which include Alzheimer’s disease and Parkinson’s disease are the result of the build up of intracellular dysfunctional proteins such as amyloid-beta and alpha-synuclein (Jucker and Walker 2011 Irregular prion protein (PrPSc) has also been shown to be a pathogenic protein which is definitely created by conformational changes to the native cellular prion protein (PrPC) (Weissmann et al. 2002 The molecular mechanisms of conversion remain poorly recognized although drug finding studies have focused on the conversion process from PrPC and PrPSc. A variety of drugs have been reported to reduce PrPSc levels by halting the conversion process as explained below: acridines including quinacrine (Vogtherr et al. 2003 anti-PrP antibodies including D18 (Peretz et al. 2001 6 (Enari Schisantherin B et al. 2001 and ICSM38 (White colored et al. 2003 polyanions including pentosane polysulfate (PPS) (Doh-ura et al. 2004 Priola and Caughey 1994 dextran sulfate (Caughey and Raymond 1993 and HM2602 (Adjou et al. 2003 the polyene antibiotics including amphotericin B (Mange et al. 2000 and filipin (Marella et al. 2002 the others including suramin (Gilch et al. 2001 Congo-Red (Caughey and Race Schisantherin B 1992 Cpd B (Kawasaki et al. 2007 GN8 (Kuwata et al. 2007 and luminescent-conjugated polythiopherenes (LCPs) (Herrmann et al. 2015 Additional studies have focused on the intracellular proteolytic system such as autophagy of insoluble proteins because the PrPSc complex and the PrP oligomer may have toxic effects within the cell (Aguzzi and Calella 2009 and studies using compounds such as lithium (Heiseke et al. 2009 trehalose (Aguib et al. 2009 rapamycin (Ishibashi et al. 2015 tamoxifen (Marzo et al. 2013 FK506 (Nakagaki et al. 2013 IU-1 (Homma et al. 2015 have reported anti-prion effects. Among them PPS Cpd B LCPs and FK506 significantly prolong survival periods in mice inoculated with RML or FK-1 prion strains (Doh-ura et al. 2004 Herrmann et al. 2015 Kawasaki et al. 2007 Nakagaki et al. 2013 Recently it especially has been reported that Anle138b offers potent and broad spectrum activity for different protein aggregation disease models (Wagner et al. 2013 Studies have Schisantherin B continued to identify suitable compounds for treating the diseases although none possess provided any Schisantherin B evidence of benefits against human being prion disease even though some were tested in clinical tests (Tsuboi et al. 2009 Haik et al. 2014 The structure-based drug finding (SBDD) using computer simulation was recently facilitated to develop effective chemical compounds. This novel approach is based on virtual screening for drug discovery and offers successfully identified compounds for treating several diseases such as nelfinavir (Kaldor et al. 1997 and amprenavir (Highleyman 1999 for AIDS; zanamivir Schisantherin B for influenza (McCauley 1999 celecoxib (Stratton and Alberts 2002 and rofecoxib (Mardini and FitzGerald 2001 as cyclooxygenase 2 inhibitors; antibacterial providers (Simmons et al. 2010 Ras inhibitor for human being malignancy (Shima et al. 2013 SBDD has also been used in prion disease showing that Cp-60 ??62 compounds that mimic the dominant negative PrPC mutant inhibit PrPSc formation (Perrier et al. 2000 and that GN8 strongly stabilises normal conformation by binding to a specific region in TSPAN32 PrPC which suppresses PrPSc production and prolongs survival of prion-infected mice (Kuwata et al. 2007 Furthermore additional small compounds that target the same position as the connection between GN8 and PrPC have been discovered by virtual screening which used initial docking simulation and those compounds reduced PrPSc levels in RML prion-infected cells (Hyeon et al. 2015 With this study we performed initial docking simulations termed Nagasaki University or college Docking Engine (NUDE) for PrPC conformation and small compounds in a large chemical compound database using the DEGIMA supercomputer system. Binding interactions were analysed using the fragment molecular orbital (FMO) method to identify novel anti-prion drugs. Following virtual screening we.