Selective PARP1 inhibitors, PARP1-based dual-target inhibitors, PROTAC PARP1 degraders, and prodrugs of PARP1 inhibitors for cancer therapy

Bibliometric analysis of research trends on the combination of immune checkpoint inhibitors and PARP inhibitors in solid tumors

“…First, improvement of the efficacy and safety of the combined therapy requires further evaluation in the future clinical studies, aiming to enhance the efficiency and decrease the chances of toxic adverse effects. For example, the development of selective PARPi in preclinical studies have demonstrated higher potency which may provide better clinical efficacy and broader spectrum of treatment [ 105 , 106 ]. Second, it is critical to screen and target the patient groups that benefit the most from the combination therapy.…”

PROTACs: A novel strategy for cancer drug discovery and development

“…cIAP1, cIAP2, and X‐chromosome‐linked IAP (XIAP) belong to the family of antiapoptotic proteins that play a critical role in the control of apoptotic machinery 354–361 . The widespread use of IAPs as an E3 ligase in TPD has drawn much attention from scientists in both academia and industry 362–368 . Correspondingly, many IAPs inhibitors were discovered and applied in the design of PROTAC degraders 284 .…”

“… 354 , 355 , 356 , 357 , 358 , 359 , 360 , 361 The widespread use of IAPs as an E3 ligase in TPD has drawn much attention from scientists in both academia and industry. 362 , 363 , 364 , 365 , 366 , 367 , 368 Correspondingly, many IAPs inhibitors were discovered and applied in the design of PROTAC degraders. 284 Specifically, the pink moiety is exposed to the solvent as a potentially ideal linking position in the design of PROTAC degraders, based on the crystal structure of IAPs inhibitor with IAPs protein (Figure 5 ; PDB ID: 5M6H).…”

Discovery, Synthesis, and Evaluation of Novel Dual Inhibitors of a Vascular Endothelial Growth Factor Receptor and Poly(ADP-Ribose) Polymerase for BRCA Wild-Type Breast Cancer Therapy

“…Practically, many excellent reviews about novel dualtarget inhibitors based on PARP (including PARP-HDAC, PARP-EZH2, PARP-PI3K, PARP-BRD4, and PARP-TNKS1) have been published. 28,29 However, there are no previous studies on dual inhibitor of VEGFR and PARP. Based on these findings, we speculated that dual VEGFR/PARP inhibitors would effectively block the progression of BRCA wild-type BC through concomitantly suppressing the expression of VEGFR and PARP and become a promising treatment strategy for tumor treatment.…”

“…To date, numerous studies have confirmed the therapeutic effect of PARP-based dual-target drugs in a variety of tumors. Practically, many excellent reviews about novel dual-target inhibitors based on PARP (including PARP-HDAC, PARP-EZH2, PARP-PI3K, PARP-BRD4, and PARP-TNKS1) have been published. , However, there are no previous studies on dual inhibitor of VEGFR and PARP. Based on these findings, we speculated that dual VEGFR/PARP inhibitors would effectively block the progression of BRCA wild-type BC through concomitantly suppressing the expression of VEGFR and PARP and become a promising treatment strategy for tumor treatment. , Notably, dual-target drugs are highly explored due to their potency, fewer drug–drug interactions, more predictable pharmacokinetic profiles, less adverse reactions, and excellent patient compliance. , Thus, identifying VEGFR/PARP dual inhibitor to leverage synthetic lethal relationships specific to BRCA wild-type BC may exert a promising treatment strategy for BC therapy.…”