title: Multiclass comparative virtual screening to identify novel Hsp90 inhibitors: a therapeutic breast cancer drug target.
abstract: Since the discovery of Hsp90, a decade ago, it has surfaced as a potential target in breast cancer therapy along with other cancers. In present study, we have selected seven established Hsp inhibitors viz., PU3, CCT-018159, CNF-2024, SNX-5422, NVP (AUY-922), EGCG and IPI-504 used in the treatment of cancer. Considering these seven inhibitors as a parent compound, ligand based search was carried out with 90% similarity in Pubchem database (31 million compounds). All the similar molecules belonging to respective parent compound along with similar compound were subjected to virtual screening using MolDock and PLP algorithm aided molecular docking. Compounds with highest docking rerank scores were selected and filtered through Lipinski's drug-likeness filters and toxicity parameters. New candidate (Pubchem CID: 11363378) qualified to demonstrate considerable affinity towards Hsp90. The selected compound was further pharmcophorically incited for receptor- ligand interactions like H-bond, electrostatic, hydrophobic interactions etc.
authors.forename: Nageswara Rao
authors.initials: NR
authors.lastname: Dunna
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
authors.forename: Uday Raj
authors.initials: UR
authors.lastname: Akare
authors.forename: Siddheshwar
authors.initials: S
authors.lastname: Rajadhyax
authors.forename: Venkata Ravi
authors.initials: VR
authors.lastname: Gutlapalli
authors.forename: Mukesh
authors.initials: M
authors.lastname: Yadav
authors.affiliation: In silico Research Laboratory, Eminent Biosciences, Vijaynagar, Indore - 452010, India. anuraj@eminentbio.com.
authors.forename: Anuraj
authors.initials: A
authors.lastname: Nayarisseri
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry; D000840:Anisoles / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives / Q000737:chemistry; D062126:Databases, Chemical; D055808:Drug Discovery; D005260:Female; D015870:Gene Expression; D005998:Glycine; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry; D057166:High-Throughput Screening Assays; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007191:Indazoles / Q000737:chemistry; D008024:Ligands; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: C521963:6-chloro-9-(4-methoxy-3,5-dimethylpyridin-2-ylmethyl)-9H-purin-2-ylamine; C494601:9-(n-butyl)-8-((3,4,5-trimethoxyphenyl)methyl)adenine; D000840:Anisoles; D000970:Antineoplastic Agents; D001549:Benzamides; C506244:CCT018159; D018841:HSP90 Heat-Shock Proteins; D006574:Heterocyclic Compounds, 2-Ring; D007191:Indazoles; D008024:Ligands; D011720:Pyrazoles; D011725:Pyridines; D002392:Catechin; C561943:SNX-5422; C045651:epigallocatechin gallate; D000225:Adenine; D005998:Glycine