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 ΔG_bind (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.

近年来，药物对聚（ADP-核糖）聚合酶（PARP）酶的抑制作为一种抗癌疗法引起了广泛关注。据报道，已发现 PARP-16 作为小细胞肺癌的新型抗癌靶点，并且他拉唑帕尼对 PARP-16 和 PARP-1 的抑制可以提高他拉唑帕尼在 SCLC 治疗中的整体有效性。在这项研究中，我们采用计算方法来研究他拉唑帕尼对 PARP-1 和 PARP-16 的不同抑制效力。Talazoparib 具有优异的 PARP-1 和 PARP-16 结合活性，如 ΔG_结合所示（总结合能）。pp16-tpb的结合能为-34.85 kcal/mol，而pp1-tpb的结合能为-26.36 kcal/mol。Talazoparib 对 PARP-1 和 PARP-16 的结合活性受到范德华和静电相互作用的显着影响。相应地，根据本研究的结果，总结合能大于 1.00 kcal/mol 的结合残基对 Talazoparib 对 PARP-1 和 PARP-16 的结合活性有很大贡献。我们相信这项研究的结果将为开发 PARP 酶的双重靶向作为小细胞肺癌治疗的策略铺平道路。