Synthesis of novel dual target inhibitors of PARP and EGFR and their antitumor activities in triple negative breast cancers

Lin, Shujing; Zhang, Xiao; Yu, Zelei; Huang, Xiuwang; Xu, Jianhua; Liu, Yang; Wu, Lixian

doi:10.1016/j.bmc.2022.116739

Cited by 10 publications

(9 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, EGFR is a promising target for developing effective agents for cancer chemotherapy . EGFR is overexpressed in the majority of triple-negative breast cancers (TNBCs), making EGFR inhibitors attractive targets for TNBC treatment . PARP inhibitors have been approved for the treatment of TNBC.…”

Section: Dual-targeting Inhibition Based On Parp and Other Anti-tumor...mentioning

confidence: 99%

“…PARP inhibitors have been approved for the treatment of TNBC. Therefore, simultaneously inhibiting PARP and EGFR may play a synergistic role in TNBC treatment. , In addition, cancer cells with EGFR mutant have been proven to be sensitive to 2 both in vitro and in vivo . Thus, simultaneous inhibition of both PARP and EGFR may act synergistically for treatment of EGFR mutant cancer cells.…”

Section: Dual-targeting Inhibition Based On Parp and Other Anti-tumor...mentioning

confidence: 99%

“…Considering that pyridine derivatives exhibited preferable antitumor activities against many cancer cells by inhibiting ATX and EGFR, 170 they attempted to introduce tetrahydropyrido [4,3-d]pyrimidines, such as 6-chloro-5,6,7,8-tetrahydropyrido [4,3d]pyrimidine (51), instead of the cyclopropanecarbonyl moiety, which is unessential for PARP inhibition, to obtain a series of novel dual PARP/EGFR inhibitors, 52a−52j (Figure 26). 168 In addition, A. Abbas's team employed thiadiazine and triazole as twin drugs against PARP-1 and EGFR by considering that some triazole-and thiadiazine-based compounds, such as 53a, exhibited promising EGFR and PARP-1 inhibition. Then, a series of compounds, 53b−53m, were obtained (Figure 26).…”

Section: Dual-targeting Inhibition Strategiesmentioning

confidence: 99%

See 2 more Smart Citations

Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

et al. 2022

View full text Add to dashboard Cite

The nuclear enzymes called poly(ADP-ribose)polymerases (PARPs) are known to catalyze the process of PARylation, which plays a vital role in various cellular functions. They have become important targets for the discovery of novel antitumor drugs since their inhibition can induce significant lethality in tumor cells. Therefore, researchers all over the world have been focusing on developing novel and potent PARP inhibitors for cancer therapy. Studies have shown that PARP inhibitors and other antitumor agents, such as EZH2 and EGFR inhibitors, play a synergistic role in cancer cells. The combined inhibition of PARP and the targets with synergistic effects may provide a rational strategy to improve the effectiveness of current anticancer regimens. In this Perspective, we sum up the recent advance of PARP-targeted agents, including single-target inhibitors/degraders and dual-target inhibitors/degraders, discuss the fundamental theory of developing these dual-target agents, and give insight into the corresponding structure–activity relationships of these agents.

show abstract

Section: Dual-targeting Inhibition Based On Parp and Other Anti-tumor...mentioning

confidence: 99%

Section: Dual-targeting Inhibition Based On Parp and Other Anti-tumor...mentioning

confidence: 99%

Section: Dual-targeting Inhibition Strategiesmentioning

confidence: 99%

See 1 more Smart Citation

Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Anti-breast cancer compounds 77, were synthesized by S. Lin et al, 65 via the reaction of chloro atom on pyrimidine nucleus with different amines using triethyl amine as a catalyst and tetrahydrofuran as a solvent. The reaction showed replacing the chloride atom with alkyl moiety (Scheme 32).…”

Section: Synthesis and Reaction Of Pyrimidines Synthesis And Reaction...mentioning

confidence: 99%

Pyrimidines as Anticancer and Antiviral: Synthesis & Reactions (A Review)

Fatahala

Mohamed²,

Khodair³

et al. 2022

Journal of Advanced Pharmacy Research

View full text Add to dashboard Cite

Background:The interest of many medicinal and organic chemists has been attracted to the synthesis of pyrimidines and their analogues due to their highly biological and medicinal properties. Objectives& Methodology: Based on these activities, this review discusses the various recent methods for the synthesis of these heterocyclic compounds during the period of 2017 to 2021 with certain two main medicinal actions. Conclusion: Pyrimidine moiety bearing compounds, are synthesized, and reacted either through one-pot synthesis or multi-step synthesis pathways, in catalytic and solvent free condition or using catalysts and solvent.

show abstract

“…Other oncogenic targets such as EGFR could be used in conjunction with PARP. 40 Lin et al 2022, 41 designed a potential PARP/EGFR dual inhibitor through pharmacophore combination using Olaparib as a clinically approved drug for PRAP-1 inhibitor. Additionally, PARP-1 inhibitors showed selective sensitivity to EGFR, hence dual inhibition targets of PARP-1/EGFR were a promising therapeutic target against cancers including breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of new bis(1,2,4-triazolo[3,4-b][1,3,4]thiadiazines) and bis((quinoxalin-2-yl)phenoxy)alkanes as anti-breast cancer agents through dual PARP-1 and EGFR targets inhibition

et al. 2022

View full text Add to dashboard Cite

show abstract

Synthesis of novel dual target inhibitors of PARP and EGFR and their antitumor activities in triple negative breast cancers

Cited by 10 publications

References 20 publications

Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

Multi-therapies Based on PARP Inhibition: Potential Therapeutic Approaches for Cancer Treatment

Pyrimidines as Anticancer and Antiviral: Synthesis & Reactions (A Review)

Design and synthesis of new bis(1,2,4-triazolo[3,4-b][1,3,4]thiadiazines) and bis((quinoxalin-2-yl)phenoxy)alkanes as anti-breast cancer agents through dual PARP-1 and EGFR targets inhibition

Contact Info

Product

Resources

About