Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers

Pharmacological Research, Journal Year: 2018, Volume and Issue: 139, P. 395 - 411

Published: Nov. 27, 2018

Language: Английский

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A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy

Bioorganic Chemistry, Journal Year: 2020, Volume and Issue: 99, P. 103811 - 103811

Published: April 2, 2020

Language: Английский

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Receptor Tyrosine Kinase-Targeted Cancer Therapy

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(11), P. 3491 - 3491

Published: Nov. 6, 2018

In the past two decades, several molecular targeted inhibitors have been developed and evaluated clinically to improve survival of patients with cancer. Molecular inhibit activities pathogenic tyrosine kinases. Particularly, aberrant receptor kinase (RTK) activation is a potential therapeutic target. An increased understanding genetics, cellular biology structural has led development numerous important therapeutics. Pathogenic RTK mutations, deletions, translocations amplification/over-expressions identified are currently being examined for their roles in cancers. Therapies targeting RTKs categorized as small-molecule monoclonal antibodies. Studies underway explore abnormalities 20 types subfamilies cancer or other diseases. this review, we describe representative developing therapeutics predicting resistance mechanisms.

Language: Английский

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Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Sept. 6, 2023

Abstract Undruggable proteins are a class of that often characterized by large, complex structures or functions difficult to interfere with using conventional drug design strategies. Targeting such undruggable targets has been considered also great opportunity for treatment human diseases and attracted substantial efforts in the field medicine. Therefore, this review, we focus on recent development discovery targeting “undruggable” their application clinic. To make review well organized, discuss strategies proteins, including covalent regulation, allosteric inhibition, protein–protein/DNA interaction targeted nucleic acid-based approach, immunotherapy others.

Language: Английский

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Discovery of Potent and Selective Epidermal Growth Factor Receptor (EGFR) Bifunctional Small-Molecule Degraders

Journal of Medicinal Chemistry, Journal Year: 2020, Volume and Issue: 63(3), P. 1216 - 1232

Published: Jan. 2, 2020

Several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed and approved by Food Drug Administration for the treatment of non-small-cell lung cancers, but their efficacy can be compromised acquired drug resistance conferred EGFR-mutant variants. Here, we described discovery a novel E3 ligase von Hippel–Lindau-recruiting EGFR degrader, MS39 (compound 6), first-in-class cereblon-recruiting MS154 10), using proteolysis targeting chimera technology. These compounds potently induced degradation mutant not wild-type in an ligase-dependent manner cancer cell lines effectively suppressed cells compared with corresponding negative controls. The global proteomic analyses revealed that were highly selective EGFR. Furthermore, both bioavailable mouse pharmacokinetic studies, compound 6 is first degrader suitable vivo studies. Overall, provide set well-characterized chemical tools to research community.

Language: Английский

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PI3K inhibitors: review and new strategies

Chemical Science, Journal Year: 2020, Volume and Issue: 11(23), P. 5855 - 5865

Published: Jan. 1, 2020

The search is on for effective specific inhibitors PI3Kα mutants.

Language: Английский

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Acquired resistance to third-generation EGFR-TKIs and emerging next-generation EGFR inhibitors

The Innovation, Journal Year: 2021, Volume and Issue: 2(2), P. 100103 - 100103

Published: April 3, 2021

The discovery that mutations in the EGFR gene are detected up to 50% of lung adenocarcinoma patients, along with development highly efficacious epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), has revolutionized treatment this frequently occurring malignancy. Indeed, clinical success these TKIs constitutes a critical milestone targeted cancer therapy. Three generations EGFR-TKIs currently approved for mutation-positive non-small cell (NSCLC). first-generation include erlotinib, gefitinib, lapatinib, and icotinib; second-generation ErbB family blockers afatinib, neratinib, dacomitinib; whereas osimertinib, by FDA on 2015, is third-generation TKI targeting harboring specific mutations. Compared first- TKIs, display significant advantage terms patient survival. For example, median overall survival NSCLC patients receiving osimertinib reached 38.6 months. Unfortunately, however, like other therapies, new mutations, as well additional drug-resistance mechanisms emerge rapidly after treatment, posing formidable obstacles therapeutics aimed at surmounting chemoresistance. In review, we summarize molecular underlying resistance ongoing efforts address overcome We also discuss current status fourth-generation inhibitors, which great value overcoming appear have greater therapeutic benefits clinic.

Language: Английский

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Molecular and functional imaging in cancer-targeted therapy: current applications and future directions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Feb. 27, 2023

Targeted anticancer drugs block cancer cell growth by interfering with specific signaling pathways vital to carcinogenesis and tumor rather than harming all rapidly dividing cells as in cytotoxic chemotherapy. The Response Evaluation Criteria Solid Tumor (RECIST) system has been used assess response therapy via changes the size of target lesions measured calipers, conventional anatomically based imaging modalities such computed tomography (CT), magnetic resonance (MRI), other methods. However, RECIST is sometimes inaccurate assessing efficacy targeted because poor correlation between treatment-induced necrosis or shrinkage. This approach might also result delayed identification when does confer a reduction size. Innovative molecular techniques have gained importance dawning era they can visualize, characterize, quantify biological processes at cellular, subcellular, even level anatomical level. review summarizes different pathways, various techniques, developed probes. Moreover, application for evaluating treatment related clinical outcome systematically outlined. In future, more attention should be paid promoting translation sensitivity biocompatible particular, multimodal technologies incorporating advanced artificial intelligence comprehensively accurately cancer-targeted therapy, addition RECIST-based

Language: Английский

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Targeting cytokine and chemokine signaling pathways for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

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Identification of 5-nitroindazole as a multitargeted inhibitor for CDK and transferase kinase in lung cancer: a multisampling algorithm-based structural study

Molecular Diversity, Journal Year: 2023, Volume and Issue: 28(3), P. 1189 - 1202

Published: April 14, 2023

Language: Английский

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