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Your search keyword '"Yang, Yingying"' showing total 6 results
Start Over Author "Yang, Yingying" Journal european journal of medicinal chemistry
6 results on '"Yang, Yingying"'

4. Synthesis and in vivo SAR study of indolin-2-one-based multi-targeted inhibitors as potential anticancer agents

Author

Yang Yingying, Zheng Qingmei, Zhao Shuyong, Zhou Haojie, Xingjiang Gong, Fan Chuanwen, and Zhang Long

Subjects
Indoles, Antineoplastic Agents, Pharmacology, Mice, Structure-Activity Relationship, In vivo, Cell Line, Tumor, Drug Discovery, Sunitinib, medicine, Animals, Humans, Structure–activity relationship, Potency, Pyrroles, Protein Kinase Inhibitors, Cell Proliferation, Dose-Response Relationship, Drug, Molecular Structure, Cell growth, Chemistry, Kinase, Organic Chemistry, Cancer, Neoplasms, Experimental, General Medicine, medicine.disease, In vitro, embryonic structures, Toxicity, cardiovascular system, Drug Screening Assays, Antitumor, HT29 Cells, Protein Kinases
Abstract

A series of indolin-2-one analogues were designed and synthesized, and all of them exhibited excellent in vitro potency. The structure and in vivo activity or toxicity relationship (in-vivo SAR) investigation of indolin-2-one structural analogues was carried out. In vivo efficacy studies indicated that 3b significantly suppressed tumor growth in HT-29 and NCI-H460 xenografts without causing significant loss of body weight. Kinase assay showed that compound 3b effectively inhibited the VEGFR-2, VEGFR-3, FLT3, Ret and PDGFR-β kinases, but had little effect on the VEGFR-1 kinase. Besides, 3b showed higher selectivity for VEGFR-2 compared with PDGFR-β. On the basis of its selectivity and safety properties, 3b was identified as a drug candidate for the treatment of cancer.

Published
2014

5. Structure-activity study of quinazoline derivatives leading to the discovery of potent EGFR-T790M inhibitors

Author

Fan Chuanwen, Zhou Haojie, Zhang Long, Yang Yingying, Zhao Shuyong, Li Yuhao, Zheng Qingmei, Zheng Shansong, and Chen Dong

Subjects
Afatinib, Mice, Nude, Antineoplastic Agents, Pharmacology, Mice, Structure-Activity Relationship, Pharmacokinetics, In vivo, Cell Line, Tumor, Drug Discovery, medicine, Structure–activity relationship, Potency, Animals, Humans, Protein Kinase Inhibitors, EGFR inhibitors, Cell Proliferation, Mice, Inbred BALB C, Dose-Response Relationship, Drug, Molecular Structure, Chemistry, Drug discovery, Organic Chemistry, General Medicine, Neoplasms, Experimental, Xenograft Model Antitumor Assays, Bioavailability, ErbB Receptors, Quinazolines, Female, medicine.drug
Abstract

We have developed a series of 6, 7-disubstituted-4-(arylamino) quinazoline derivatives that functioned as irreversible EGFR inhibitors, and these compounds exhibited excellent enzyme inhibition potency. As compared with afatinib, some of them showed significantly enhanced activities towards H1975 cells (EGFR-T790M). Furthermore, the optimized compounds 7q and 8f also demonstrated good pharmacokinetic profiles, oral bioavailability as well as excellent in vivo efficacy in H1975 and HCC827 xenografts at a non-toxic dose. Based on the improved safety and efficacy against EGFR-T790M resistance, 7q and 8f are promising candidates for further studies.

Published
2014

6. Discovery of a potent dual EGFR/HER-2 inhibitor L-2 (selatinib) for the treatment of cancer

Author

Yang Yingying, Zongru Guo, Shaobo Yang, Fan Chuanwen, Jianrong Zhu, Lin Dong, Zhang Long, Zhao Shuyong, and Ying Li

Subjects
Male, Receptor, ErbB-2, Druggability, Antineoplastic Agents, Pharmacology, Lapatinib, Mice, Structure-Activity Relationship, In vivo, Neoplasms, Drug Discovery, medicine, Structure–activity relationship, Animals, Humans, Rats, Wistar, skin and connective tissue diseases, Cell Proliferation, Mice, Inbred BALB C, Aniline Compounds, Dose-Response Relationship, Drug, Molecular Structure, Cell growth, Drug discovery, Chemistry, Organic Chemistry, Cancer, General Medicine, Neoplasms, Experimental, medicine.disease, Bioavailability, Rats, ErbB Receptors, Solubility, Quinazolines, Female, Drug Screening Assays, Antitumor, medicine.drug
Abstract

To develop potent dual EGFR/HER-2 inhibitors with improved druggability, a series of new lapatinib analogs were designed and synthesized. Compared with lapatinib, L-2, L-4 and M-6 were more active against BT-474 or NCI-N87 cells. In vivo efficacy studies indicated that L-2 significantly suppressed tumor growth in NCI-N87 (94.8% inhibition) or SK-OV-3 xenograft (85.7% inhibition) without causing significant loss of body weight. And the inhibition rates of lapatinib in the two xenograft models were 89.7% and 78.8%, respectively. Moreover, further studies revealed that the potent in vivo activities of L-2 may be mainly attributed to its superior aqueous solubility and oral bioavailability. In addition, a high-yielding one-pot procedure was developed for the synthesis of lapatinib and its analogs.

Published
2013

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