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

Mgoboza, Chwayita; Okunlola, Felix O.; Akawa, Oluwole B.; Aljoundi, Aimen; Agoni, Clement

doi:10.1007/s12013-022-01075-3

Cited by 3 publications

(1 citation statement)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study has indicated varying binding profiles among PARP inhibitors like Niraparib, Olaparib, Rucaparib, Veliparib, 33 and Talazoparib. 34 This additional activity holds potential for clinical benefit as suggested for talazoparib, 35,36 unveiling primary protein targets, as well as potential beneficial off-targets and guiding the design of selective and potent new inhibitors and PROTAC molecules.…”

Section: ■ Discussionmentioning

confidence: 99%

A Tandem-Affinity Purification Method for Identification of Primary Intracellular Drug-Binding Proteins

Islam,

Gour,

Beer

et al. 2024

ACS Chem. Biol.

View full text Add to dashboard Cite

In the field of drug discovery, understanding how small molecule drugs interact with cellular components is crucial. Our study introduces a novel methodology to uncover primary drug targets using Tandem Affinity Purification for identification of Drug-Binding Proteins (TAP-DBP). Central to our approach is the generation of a FLAG-hemagglutinin (HA)-tagged chimeric protein featuring the FKBP12(F36V) adaptor protein and the TurboID enzyme. Conjugation of drug molecules with the FKBP12(F36V) ligand allows for the coordinated recruitment of drug-binding partners effectively enabling in-cell TurboID-mediated biotinylation. By employing a tandem affinity purification protocol based on FLAG-immunoprecipitation and streptavidin pulldown, alongside mass spectrometry analysis, TAP-DBP allows for the precise identification of drug-primary binding partners. Overall, this study introduces a systematic, unbiased method for identification of drug−protein interactions, contributing a clear understanding of target engagement and drug selectivity to advance the mode of action of a drug in cells.

show abstract