Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC

Peng, Fan-Wei; Ji, Xuan; Wu, Tong; Xue, Jia‐Yu; Ren, Ziwei; Liu, Dake; Wang, Xiuqi; Chen, Xin-Hang; Zhang, Jiawei; Xu, Yungen; Shi, Lei

doi:10.1016/j.ejmech.2015.12.033

Cited by 65 publications

(40 citation statements)

References 41 publications

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“…Hybrid 38a showed IC 50 of 1.2 μM against human breast cancer cell line MCF‐7 compared to 4.5 and 18.5 μM of the parent SAHA and vandetanib, respectively. In 2016, they developed the more potent compound 38b containing para bromo substitution (Figure ). Hybrid 38b showed potent cytotoxic activity with IC 50 of 0.85 μM on MCF‐7 cell line rendering a valuable start for further structural optimization using different linker, rather than the aliphatic chain or using aryl linker.…”

Section: Design Of Dual Protein Tyrosine Kinase (Ptk) Hdac Inhibitorsmentioning

confidence: 99%

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Hesham

Lasheen

Abouzid

2018

Medicinal Research Reviews

122

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Recently, molecular hybridization paradigm became an interesting and smart way to defeat the multifaceted cancer disease by a single molecular entity that acts via several mechanisms just like a magic bullet. Also, HDAC is an important epigenetic target in drug discovery, and the HDAC inhibitors showed successful pattern as cytotoxic agents. Because of their flexible structure activity relationship, it was easy to link them to other anticancer scaffolds. So, many dual action HDAC inhibitors have been developed and most of these hybrids have higher potency than the constituting parents in fighting of the cancer cells. This review describes potential applications of chimeric HDAC inhibitors, which simultaneously modulate not only HDAC but also multiple targets, in treatment of relapsing and drug-resistant cancers. We have nearly collected most of the reported dual action HDAC inhibitors yet to provide a comprehensive guide for the drug discovery process for developing more efficient anticancer agents.

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Section: Design Of Dual Protein Tyrosine Kinase (Ptk) Hdac Inhibitorsmentioning

confidence: 99%

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Hesham

Lasheen

Abouzid

2018

Medicinal Research Reviews

122

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“…CUDC‐101 was more potent (IC 50 = 0.55 μmol/L) than the combination of the parent drugs erlotinib + vorinostat (2.7 μmol/L) in MCF‐7 cells and promoted tumor inhibition in various cancer xenograph models including breast cancer . Other dual protein tyrosine kinase—HDAC inhibitors (Table ) that were reported to display higher or equal cytotoxicity compared to the parent agents in various breast cancer cell lines include hybrids of ribociclib (CDK‐4 inhibitor) and vorinostat, FGFR‐1‐inhibitor and nexturastat, ruxolitinib (Janus kinase inhibitor)‐vorinostat, vandetanib (VEGFR inhibitor)–vorinostat, casein kinase 2 inhibitor and triazole hydroxamic acid (HDAC inhibitor), semaxanib (VEGFR inhibitor) and vorinostat, c‐Src kinase inhibitor and vorinostat, and lapitanib (EGFR inhibitor) and panabinostat …”

Section: Pharmacology Of Drug‐drug Conjugatesmentioning

confidence: 99%

Drug conjugates—an emerging approach to treat breast cancer

Hasan

Leak

Stratford

et al. 2018

Pharmacology Res & Perspec

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Breast cancer treatment using a single drug is associated with a high failure rate due, in part, to the heterogeneity of drug response within individuals, nonspecific target action, drug toxicity, and/or development of resistance. Use of dual‐drug therapies, including drug conjugates, may help overcome some of these roadblocks by more selective targeting of the cancer cell and by acting at multiple drug targets rather than one. Drug‐conjugate approaches include linking drugs to antibodies (antibody‐drug conjugates), radionuclides (radioimmunoconjugates), nanoparticles (nanoparticle‐drug conjugates), or to other drugs (drug‐drug conjugates). Although all of these conjugates might be designed as effective treatments against breast cancer, the focus of this review will be on drug‐drug conjugates because of the increase in versatility of these types of drugs with respect to mode of action at the level of the cancer cell either by creating a novel pharmacophore or by increasing the potency and/or efficacy of the drugs’ effects at their respective molecular targets. The development, synthesis, and pharmacological characteristics of drug‐drug conjugates will be discussed in the context of breast cancer with the hope of enhancing drug efficacy and reducing toxicities to improve patient quality of life.

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“…Относительно недавно опубликован ряд примеров бифункциональных VEGFR-2/HDACингибиторов [Peng et al, 2015;Peng et al, 2016].…”

Section: Introductionunclassified

Quantitative analysis of "structure - anticancer activity" and rational molecular design of bi-functional VEGFR-2/HDAC-inhibitors

Tinkov¹,

Polishchuk²,

Khachatryan³

et al. 2019

CRM

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Design, synthesis and biological evaluation of N-phenylquinazolin-4-amine hybrids as dual inhibitors of VEGFR-2 and HDAC

Cited by 65 publications

References 41 publications

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Chimeric HDAC inhibitors: Comprehensive review on the HDAC‐based strategies developed to combat cancer

Drug conjugates—an emerging approach to treat breast cancer

Quantitative analysis of "structure - anticancer activity" and rational molecular design of bi-functional VEGFR-2/HDAC-inhibitors

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