Tankyrase Inhibitor for Cardiac Tissue Regeneration: an In-silico Approach.

Abstract

Myocardial infarction causes heart tissue damages; therefore, using non-invasive methods to regenerate the heart tissue could be very helpful. Recent studies claimed that the inhibition of the Wnt signaling could promote cardiac remodeling and induce cardiac regeneration. Therefore, a tankyrase inhibitor to stabilize the AXIN and inhibit the Wnt/β-catenin signaling pathway will induce cardiac regeneration after injury. In this regard, virtual screening procedure, using molecular docking of 9127 FDA and world approved drugs, including herbal medicine, was done over the crystal structures of tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) catalytic poly (ADP-ribose) polymerase (PARP) domains with PDB ID: 2RF5 and 3KR7, respectively, to find potential small molecule inhibitors to regenerate injured heart tissue. Subsequently, molecular dynamics simulations were done to assess the stability of selected ligands phenothrin and ethyl rosinate in the binding pocket of TNKS1 and TNKS2 for 100 ns, respectively. Both compounds show suitable interaction in their binding pocket. The molecular dynamics simulation results confirm their stability. The binding free energy of complexes was carried out by the MM-PBSA method. ADME properties also indicate the potential of drug-likeness of both compounds. Taking together both drugs may be promising for inducing cardiac regeneration after injury. Nevertheless, clinical approval remains.