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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

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Abstract

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.

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Authors and Affiliations

  1. Molecular Bio-computation and Drug Design Laboratory, School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, 4001, South Africa

    Chwayita Mgoboza, Felix O. Okunlola, Oluwole B. Akawa, Aimen Aljoundi & Mahmoud E. S. Soliman

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  1. Chwayita Mgoboza
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  2. Felix O. Okunlola
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  3. Oluwole B. Akawa
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  4. Aimen Aljoundi
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  5. Mahmoud E. S. Soliman
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Correspondence to Mahmoud E. S. Soliman.

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Mgoboza, C., Okunlola, F.O., Akawa, O.B. et al. 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. Cell Biochem Biophys 80, 495–504 (2022). https://doi.org/10.1007/s12013-022-01075-3

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