Backgound: Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in the process of cancer angiogenesis. Type I inhibitors constitute the major ATP-competitive inhibitors and recognize mainly the active conformation of VEGFR-2. Meanwhile, type II inhibitors recognize the inactive DFG (Asp-Phe-Gly)-out conformation of VEGFR-2, which was a more promising approach for drug intervention. Methods: According to the lead compound of uracil skeleton, being screened out by structure-based virtual screening, a series of uracil derivatives were designed and synthesized. Results: The inhibitory activities were investigated against VEGFR-2 kinase in vitro. The results turned out that series A performed moderate inhibitory activities, especially compound A4 exhibited the most potent inhibitory activity (IC50 = 0.029 mu M). Conclusion: The lead compound was screened out by structure-based pharmacophore models, then two series of uracil derivatives were synthesized according to it and evaluated for their inhibitory activities against VEGFR-2. In this study, not only a potential inhibitor has been discovered, it also demonstrates the feasibility of structure-based virtual screening method for drug discovery.
机构:
Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Yang, Feiyi
Zhang, Qian
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
South China Univ Technol, Sch Biol Sci & Engn, Guangzhou 510641, Guangdong, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Zhang, Qian
Guo, Qiuyan
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Guo, Qiuyan
Pan, Qingshan
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Pan, Qingshan
Wen, Chunping
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Wen, Chunping
Lv, Xinya
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Lv, Xinya
Zhu, Wufu
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
Zhu, Wufu
Zheng, Pengwu
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Jiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R ChinaJiangxi Sci & Technol Normal Univ, Sch Pharm, Nanchang 330013, Jiangxi, Peoples R China
机构:
E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Yan, Wei
Huang, Zhaoru
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Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
Zhengzhou Univ, Affiliated Hosp 1, Dept Gastroenterol, Zhengzhou 450014, Henan, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Huang, Zhaoru
Wang, Zhengyu
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China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Wang, Zhengyu
Cao, Sufen
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E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Cao, Sufen
Tong, Linjiang
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Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Tong, Linjiang
Zhang, Tao
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Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Zhang, Tao
Wang, Chen
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Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Wang, Chen
Zhou, Lin
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Zhengzhou Univ, Affiliated Hosp 1, Dept Gastroenterol, Zhengzhou 450014, Henan, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Zhou, Lin
Ding, Jian
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Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Ding, Jian
Luo, Cheng
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Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Luo, Cheng
Zhou, Jinpei
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China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Zhou, Jinpei
Xie, Hua
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Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Xie, Hua
Duan, Wenhu
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E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R ChinaE China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
机构:
Al Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
El-Helby, Abdel-Ghany A.
Sakr, Helmy
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Al Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
Sakr, Helmy
Eissa, Ibrahim H.
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Al Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
Eissa, Ibrahim H.
Abulkhair, Hamada
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Al Azhar Univ, Fac Pharm, Dept Pharmaceut Organ Chem, Cairo, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
Abulkhair, Hamada
Al-Karmalawy, Ahmed A.
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Al Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
Al-Karmalawy, Ahmed A.
El-Adl, Khaled
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Al Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
Heliopolis Univ Sustainable Dev, Fac Pharm & Drug Technol, Dept Pharmaceut Chem, Cairo, EgyptAl Azhar Univ, Fac Pharm, Dept Pharmaceut Chem, 1 Al Mukhayam Al Daem St,6th Dist, Cairo 00202226257, Egypt
机构:
China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Deng, Ya-Hui
Xu, Dan
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China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Xu, Dan
Su, Ye-Xiang
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China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Su, Ye-Xiang
Cheng, Yi-Juan
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China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Cheng, Yi-Juan
Yang, Yan-Li
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China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Yang, Yan-Li
Wang, Xiu-Yun
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China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Wang, Xiu-Yun
Zhang, Juan
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China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
Zhang, Juan
You, Qi-Dong
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China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
You, Qi-Dong
Sun, Li-Ping
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China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R ChinaChina Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Peoples R China
机构:
Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Taghour, Mohammed S.
Mahdy, Hazem A.
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Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Mahdy, Hazem A.
Gomaa, Maher H.
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Al Azhar Univ, Fac Pharm Boys, Biochem & Mol Biol Dept, Cairo, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Gomaa, Maher H.
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Aglan, Ahmed
Eldeib, Mahmoud Gomaa
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Al Azhar Univ, Fac Pharm Boys, Biochem & Mol Biol Dept, Cairo, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Eldeib, Mahmoud Gomaa
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Elwan, Alaa
Dahab, Mohammed A.
论文数: 0引用数: 0
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机构:
Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Dahab, Mohammed A.
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Elkaeed, Eslam B.
Alsfouk, Aisha A.
论文数: 0引用数: 0
h-index: 0
机构:
Princess Nourah Bint Abdulrahman Univ, Coll Pharm, Dept Pharmaceut Sci, Riyadh, Saudi ArabiaAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Alsfouk, Aisha A.
Khalifa, Mohamed M.
论文数: 0引用数: 0
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Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
Khalifa, Mohamed M.
Eissa, Ibrahim H.
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Al Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, EgyptAl Azhar Univ, Fac Pharm Boys, Pharmaceut Med Chem & Drug Design Dept, Cairo 11884, Egypt
机构:
Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Huang, Yuanzheng
Zhang, Yang
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Zhang, Yang
Li, Jiaming
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Anhui Acad Chinese Med, Dept Med Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Li, Jiaming
Ma, Xiaodong
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Anhui Acad Chinese Med, Dept Med Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Ma, Xiaodong
Hu, Mengqi
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Hu, Mengqi
Yang, Yu
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China
Yang, Yu
Gao, Sufan
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Anhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R ChinaAnhui Acad Chinese Med, Sch Pharm, Dept Pharmaceut Chem, Hefei, Anhui, Peoples R China