cct018159 and epigallocatechin-gallate

Heat shock protein 90 is a new target of antitumor drug, the inhibitor of Hsp90 fight against tumor by destroy and degrade the structure of protein. In recent years, looking for Hsp90 inhibitor is not only via structure modifying of natural products, but also via high throughput screening and computer aided drug design to find and synthesize new kinds of Hsp90 inhibitor. Anyway, Hsp90 inhibitor has considered as an important biology target and to pay more and more attention. This review describes recent developments of small molecule Hsp90 inhibitors.

Topics: Adenine; Animals; Anisoles; Antineoplastic Agents; Benzoquinones; Catechin; Cell Line, Tumor; Crystallization; Heterocyclic Compounds, 2-Ring; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Macrolides; Molecular Structure; Neoplasms; Pyrazoles; Structure-Activity Relationship

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.

Topics: Adenine; Anisoles; Antineoplastic Agents; Benzamides; Binding Sites; Breast Neoplasms; Catechin; Databases, Chemical; Drug Discovery; Female; Gene Expression; Glycine; Heterocyclic Compounds, 2-Ring; High-Throughput Screening Assays; HSP90 Heat-Shock Proteins; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Indazoles; Ligands; Molecular Docking Simulation; Protein Binding; Pyrazoles; Pyridines; Static Electricity; Structure-Activity Relationship; User-Computer Interface