探索小分子 c-Met 和血管内皮生长因子受体(VEGFR)双重抑制剂在癌症治疗的进展和未来药物发现中的潜力

IF 3.4 Q2 PHARMACOLOGY & PHARMACY Future Journal of Pharmaceutical Sciences Pub Date : 2024-09-18 DOI:10.1186/s43094-024-00688-0
Sachin A. Dhawale, Arundhati V. Deokar, Momin Aaliya Firdous, Madhuri Pandit, Minal Y. Chaudhari, Sameer B. Salve, Madhuri Khandgaonkar, Mahesh Parwe, Rupesh Khalse, Shruti G. Dake, Siddharth H. Chatse, Ganesh G. Tapadiya
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引用次数: 0

摘要

背景癌症是不受控制的细胞增殖,有可能侵入其他组织和细胞。最常见的三大癌症是乳腺癌、肺癌和结肠癌。最广泛的激酶家族是受体酪氨酸激酶(RTKs),几种化疗药物都以其为靶点。血管内皮生长因子(VEGFR)是一种著名的 IV 型酪氨酸激酶受体,是开发血管生成相关癌症疗法的有效生物靶点。肝细胞生长因子(又称间充质-上皮转化因子)会引发 c-Met 酪氨酸激酶受体的活化,而 c-Met 酪氨酸激酶受体控制着包括细胞分裂、存活和增殖在内的多个生物过程。正文在这篇综述中,我们总结了各种对癌症具有治疗作用的血管内皮生长因子受体和 c-MET 受体双重抑制剂。一些血管内皮生长因子受体(VEGFR)和 c-MET 受体抑制剂的组合还显示出协同作用。已开发的血管内皮生长因子受体和 c-MET 双重抑制剂,如喹诺酮类和喹唑啉类衍生物、吡啶和嘧啶衍生物、吲哚分子和三嗪衍生物,对血管内皮生长因子受体和 c-MET 具有最强的抑制作用。血管内皮生长因子受体(VEGFR)和 c-MET 的双重抑制剂通过提高疗效、减少耐药性和改善患者预后,在改善癌症治疗方面大有可为。目前正在对其中几种化合物进行临床试验,其他化合物也在研究之中。抑制血管内皮生长因子受体(VEGFR)和 c-Met 通路的活性将作为治疗癌症的新型治疗策略进行讨论,并将进一步开发。本综述中的研究进展截止到今年。结论除了癌症治疗的发展,由于其毒性和抗药性,癌症仍被列为致命疾病。因此,有必要采用新方法来攻克癌症。作为双重抑制剂的血管内皮生长因子受体和 c-MET 抑制剂在未来的临床抗癌治疗中可能会发挥更大的作用。
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Exploring the potential of small molecules of dual c-Met and VEGFR inhibitors for advances and future drug discovery in cancer therapy

Background

Cancer is uncontrolled cell proliferation that has the potential to invade other tissues and cells. The first three most prevalent cancers are breast, lung, and colon cancer. The widest family of kinase enzymes is receptor tyrosine kinases (RTKs) which are aimed by several chemotherapy medicines. The vascular endothelial growth factor (VEGFR), a well-known type IV tyrosine kinase receptor, is an effective biological target for the development of angiogenesis-related cancer treatments. The hepatocyte growth factor (also known as mesenchymal–epithelial transition factor) triggers the activation of the c-Met tyrosine kinase receptor, which controls several biological processes including cell division, survival, and proliferation.

Main body

In this review, we summarized the various dual inhibitors of VEGFR and c-MET receptors which are active for therapeutic action against cancer. Combination of some VEGFR and c-Met inhibitors also shows synergistic action. The developed dual inhibitors of VEGFR and c-MET such as quinolones and quinazolines derivatives, pyridine and pyrimidine derivatives, oxindole moiety and triazine derivatives are most potent for the same. Dual inhibitors of VEGFR and c-MET hold significant promise in improving cancer therapy by enhancing treatment efficacy, reducing resistance, and potentially improving patient outcomes. Clinical trials are currently being conducted on a few of them and other compounds are being under investigation. Inhibiting VEGFR and c-Met pathway activity will be discussed as novel therapeutic strategies for advanced development in treating cancer. The research progress in this review is fetched up to the current year.

Conclusion

Apart from the development of cancer treatment still cancer is listed as a deadly disease, due to its toxicity and resistance to treatment. Hence, the novel approach is necessary to overcome the cancer. The VEGFR and c-MET inhibitors as dual inhibitors may be more significant in future clinical anticancer treatments.

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来源期刊
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发文量
44
审稿时长
23 weeks
期刊介绍: Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
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