Docking Studies of Bcr-Abl And c-Abl by Structural Analogues of GNF-2

In an attempt to search for new pharmacological approach to overcome resistance to ATP-binding-site inhibitors of Bcr-Abl, allosteric inhibitors had been discovered. The ATP-competitive inhibitors nilotinib and dasatinib, which bind to catalytically different conformation of the Abl kinase domain, had been approved for the targeting most of imatinib-resistant CML, fail to effectively suppress the Bcr-Abl activity of T351I (gatekeeper) mutation. The GNF-2, class of compound that inhibits Bcr-Abl kinase activity through an allosteric non-ATP competitive mechanism. The GNF-2 binds to myristate-binding site of Abl, leading to change in structure of ATP-binding-site. The GNF-5, an analogue of GNF-2 has appropriate pharmacokinetic properties, used in simultaneous binding of ATP-binding-inhibitors imatinib and nilotinib to obscure resistant mutation in Bcr-Abl. The aim of this work is to analyse the different structural analogues of GNF-2, which can be used as therapeutic agent to treat Chronic Myelogenous Leukemia (CML).

Autorentext

Pursuing M.Phil Bioinformatics from Gujarat University, Ahmedabad, India. Completed research work on cancer biology especially Chronic myelocytic leukaemia(CML) and Acute myelocytic leukaemia(AML). Presently working on the project miRNA(microRNA), targeting to treat disease in cellular level.