Talazoparib Dual-targeting on Poly (ADP-ribose) Polymerase-1 and -16 Enzymes Offers a Promising Therapeutic Strategy in Small Cell Lung Cancer Therapy: Insight from Biophysical Computations.

In recent times, inhibition of poly (ADP-ribose) polymerase (PARP) enzymes by pharmacological drugs has attracted much attention as an anticancer therapy. As reported, PARP-16 has been discovered as a novel anticancer target for small cell lung cancer, and that the inhibition of both PARP-16 and PARP-1 by talazoparib can increase the overall effectiveness of talazoparib in the SCLC treatment. In this study, we employed computational approaches to investigate the differential inhibitory potency of Talazoparib on PARP-1 and PARP-16. Talazoparib has excellent PARP-1 and PARP-16 binding activities, as revealed by the ΔGbind (total binding energy). Pp16-tpb had binding energy of -34.85 kcal/mol, while pp1-tpb had a binding energy of -26.36 kcal/mol. The binding activity of Talazoparib on both PARP-1 and PARP-16 was significantly influenced by van der Waal and electrostatic interactions. Correspondingly, according to the findings of this study, binding residues with total binding energy greater than 1.00 kcal/mol contributed considerably to the Talazoparib's binding activities on PARP-1 and PARP-16. We believe the findings of this study will pave the way for developing dual targeting of PARP enzymes as a strategy for small-cell lung cancer treatment.