Discovery of dual PARP and CDK6 inhibitors for triple-negative breast cancer with wild-type BRCA

Article Chemistry, Medicinal

Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy

Lun Tan et al.

Summary: EGFR dual-target inhibitors play an important role in the treatment of EGFR-mutant non-small-cell lung cancer by reducing drug resistance risk and improving efficacy with fewer adverse effects.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Article Chemistry, Medicinal

Discovery of 4-Hydroxyquinazoline Derivatives as Small Molecular BET/PARP1 Inhibitors That Induce Defective Homologous Recombination and Lead to Synthetic Lethality for Triple-Negative Breast Cancer Therapy

Jifa Zhang et al.

Summary: This study describes the development of a highly selective compound, BP44, targeting BRD4 and PARP1, which triggers synthetic lethality in TNBC by inhibiting homologous recombination, leading to cell cycle arrest and DNA damage. Optimizing the BRD4-PARP1 inhibitor provides a potential candidate drug for the treatment of TNBC in the future.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Article Chemistry, Medicinal

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

Jie Zhang et al.

Summary: This article summarizes the recent advances in PARP-targeted agents, discusses the basic theory of developing dual-target agents, and provides insights into the structure-activity relationships of these agents.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

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Article Pharmacology & Pharmacy

Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly(ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy

Xiaosa Chang et al.

Summary: The study successfully designed the first dual-target small-molecule inhibitor targeting both PARP1 and BRD4, showing important cross relation and synthetic lethal effect in breast cancer global network. The inhibitor exhibited good activity and therapeutic potential in breast cancer cells.

ACTA PHARMACEUTICA SINICA B (2021)

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Article Chemistry, Medicinal

Discovery of novel PARP/PI3K dual inhibitors with high efficiency against BRCA-proficient triple negative breast cancer

Junwei Wang et al.

Summary: Co-targeting PARP and PI3K with dual inhibitors is a promising strategy for treating triple negative breast cancer. Compound 12, a novel PARP/PI3K dual inhibitor, exhibits superior antiproliferative effects and excellent antitumor efficacy in animal models.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Chemistry, Medicinal

Discovery of Potent and Novel Dual PARP/BRD4 Inhibitors for Efficient Treatment of Pancreatic Cancer

Shu-Ping Wang et al.

Summary: Targeting PARP1/2 and BRD4 with the novel dual inhibitor III-16 showed promising synergistic antitumor efficacy in pancreatic cancer, suggesting it as a potential treatment option for advanced pancreatic cancer.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Chemistry, Medicinal

Discovery of novel and potent PARP/PI3K dual inhibitors for the treatment of cancer

Zhengyang Wu et al.

Summary: PARP inhibitors have shown success in cancers with BRCA mutations, but their narrow indication spectrum is limited by the small portion of patients carrying such mutations. Recent evidence suggests that the combination of PARP and PI3K inhibitors may have synergistic effects in various cancers.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Oncology

Efficacy and mechanism of the combination of PARP and CDK4/6 inhibitors in the treatment of triple-negative breast cancer

Xiuzhi Zhu et al.

Summary: The combination of PARPi olaparib and CDK4/6i palbociclib shows synergistic effects against BRCA(mut)/TNBC, especially in cells resistant to olaparib, by inhibiting HR repair, increasing DNA damage, and suppressing tumor growth.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Article Chemistry, Medicinal

Discovery of PF-06873600, a CDK2/4/6 Inhibitor for the Treatment of Cancer

Kevin D. Freeman-Cook et al.

Summary: Selective pharmacological inhibition of CDK4/6 in controlling cell cycle has shown benefits in breast cancer treatment. Expanding this approach to additional cell cycle CDK isoforms could provide benefits for patients resistant to CDK4/6 inhibitors. Through structure-based drug design and molecular dynamics simulations, PF-06873600 (22) was identified as a candidate for cancer treatment and advanced to phase 1 clinical trials.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Chemistry, Medicinal

Discovery of First-in-Class Dual PARP and EZH2 Inhibitors for Triple-Negative Breast Cancer with Wild-Type BRCA

Cheng Wang et al.

Summary: The dual action of PARP inhibitors and EZH2 inhibitors can enhance the treatment of TNBC, with the compound 5a showing potential in reducing sensitivity to inhibitors in BRCA cells.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Article Chemistry, Medicinal