Article
Biochemistry & Molecular Biology
Xin Sun, Yang Yang, Lulu Xia, Shiyu Wang, Yuxing Fu, Yuxuan Zhu, Shan Xu, Wufu Zhu, Wufu Zhu
Summary: The study investigates the effect of XIN-10, a dual PI3K/mTOR inhibitor, on the growth and antiproliferation of tumor cells. It demonstrates that XIN-10 has a potent inhibitory effect on breast cancer cells and can block the activation of the downstream mTOR pathway. These findings suggest that XIN-10 has strong potential as a novel PI3K/mTOR dual inhibitor for the treatment of breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Chuchu Li, Yuqiao Han, Zhengyang Wang, Yanan Yu, Chen Wang, Ziwei Ren, Yanzhi Guo, Tong Zhu, XuWen Li, Suzhen Dong, Mingliang Ma
Summary: Compound 42 showed excellent dual PI3K/mTOR inhibitory activity, significant in vitro and in vivo anti-tumoral activities, good kinase selectivity, low hepatotoxicity, modest plasma clearance and acceptable oral bioavailability. It is a promising PI3K/mTOR targeted anti-cancer drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Pengxing He, Jing Jing, Linna Du, Xuyang Zhang, Yufei Ren, Han Yang, Bin Yu, Hongmin Liu
Summary: YS-363 is a novel EGFR inhibitor that demonstrates potent reversible inhibition and excellent activities against cell proliferation, migration, cell cycle and apoptosis. It is a promising selective inhibitor that can potentially be developed as a more effective anti-lung cancer agent targeting EGFR.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Chemistry, Medicinal
Chengbin Yang, Yi Chen, Tianze Wu, Yunjian Gao, Xiaofeng Liu, Yongtai Yang, Yun Ling, Yu Jia, Mingli Deng, Jianxin Wang, Yaming Zhou
Summary: The PI3K-Akt-mTOR pathway is highly activated in human hematological malignancies and has shown promise as a potential target for acute myeloid leukemia (AML) therapy. In this study, we synthesized a series of 7-azaindazole derivatives as potent dual inhibitors of PI3K/mTOR, with compound FD274 showing excellent inhibitory activity. In vitro and in vivo studies demonstrated the potential of FD274 as a targeted anti-AML drug candidate.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yang Yang, Xin Sun, Leixuan Luo, Rujue Peng, Ruiqing Yang, Zhenjie Cheng, Yao Lv, Hongfeng Li, Qidong Tang, Wufu Zhu, Dan Qiao, Shan Xu
Summary: In this study, a novel class of PI3K/mTOR dual inhibitors was developed through scaffold hopping and synthesis, with compound Y-2 showing promising inhibitory effects. Pharmacological experiments confirmed the antitumor activity of Y-2, and its inhibitory effect on mTOR kinase was significantly greater than that of the reference drug GDC-0941. The study provides a valuable candidate for cancer treatment.
ARCHIV DER PHARMAZIE
(2023)
Review
Pharmacology & Pharmacy
Xianbo Wu, Yihua Xu, Qi Liang, Xinwei Yang, Jianli Huang, Jie Wang, Hong Zhang, Jianyou Shi
Summary: Studies have shown that PI3K/mTOR inhibitors are effective in cancer treatment, as they can inhibit cell proliferation and promote apoptosis. These inhibitors exhibit high potency and low drug resistance, indicating they have great potential as anticancer drugs.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Shan Xu, Xin Sun, Leixuan Luo, Yang Yang, Qiuyan Guo, Sheng Tang, Zhiyan Jiang, Yuzhen Li, Jiaqian Han, Wenhui Gan, Feiyi Yang, Xuan Zhang, Yijun Liu, Chuanchuan Sun, Jie He, Meng Liu, Daiying Zuo, Wufu Zhu, Yingliang Wu
Summary: Breast cancer has become the most commonly diagnosed cancer and there is an urgent need for effective therapeutic drugs. In this study, a novel drug XS-2 was designed and synthesized, showing potent anti-tumor activity against breast cancer cells, particularly triple-negative breast cancer (TNBC). XS-2 exhibited strong inhibitory effects on cancer cells both in vitro and in vivo, with low toxicity. Furthermore, XS-2 was found to inhibit cell invasion and migration. These findings suggest that XS-2 has the potential to be developed as a high-efficiency and low-toxicity therapeutic drug for TNBC.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Biology
Roya Gasimli, Cagla Kayabasi, Besra Ozmen Yelken, Aycan Asik, Fatma Sogutlu, Caglar Celebi, Sunde Yilmaz Susluer, Serra Kamer, Cigir Biray Avci, Ayfer Haydaroglu, Cumhur Gunduz
Summary: The study aimed to increase the sensitivity of breast cancer cells to radiotherapy by using PKI-402, a dual PI3K/mTOR inhibitor. The results showed that PKI-402 had cytotoxic effects on all cell lines and inhibited the colony formation ability of MCF-7 and breast cancer stem cell lines. Additionally, the combined use of PKI-402 and radiotherapy resulted in more apoptotic cell death in MCF-7 cells but did not significantly affect MDA-MB-231 cells.
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY
(2023)
Article
Cell Biology
I-Lun Hsin, Huang-Pin Shen, Hui-Yi Chang, Jiunn-Liang Ko, Po-Hui Wang
Summary: The study revealed a novel mechanism of the PI3K/mTOR dual inhibitor, PQR309, in lowering cell viability in endometrial cancer cells by disrupting the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop.
Article
Multidisciplinary Sciences
Omar A. El-Khouly, Morkos A. Henen, Magda A-A El-Sayed, Shahenda M. El-Messery
Summary: A new series of benzofuran derivatives were designed and synthesized, and the structures of the compounds were confirmed using various methods. Compound 8 showed the highest activity against hepatocellular and prostate cancer cell lines, with selective inhibition against PI3K and VEGFR-2.
SCIENTIFIC REPORTS
(2022)
Article
Pediatrics
Yun Chen, Huang-Wen Tsai, Ya-Hui Tsai, Sheng-Hong Tseng
Summary: This study demonstrated the antitumor effects of VS-5584 on neuroblastomas by inhibiting proliferation and inducing G0/G1 cell cycle arrest. In mouse experiments, VS-5584 significantly suppressed tumor growth in neuroblastomas.
JOURNAL OF PEDIATRIC SURGERY
(2021)
Article
Biochemistry & Molecular Biology
Shan Xu, Leixuan Luo, Xin Sun, Yang Yang, Qiuyan Guo, Zhiyan Jiang, Yingliang Wu
Summary: In this study, we developed and synthesized a series of novel thiophene-triazine derivatives containing arylurea unit as potent dual PI3K/mTOR inhibitors. We evaluated their cytotoxicity against nine cancer cell lines and their kinase inhibitory activity against PI3K/mTOR kinases. Most of the target compounds showed excellent activity and selectivity against one or more cancer cell lines. The most promising compound exhibited significantly better activity than the lead compound GDC-0941 with excellent inhibitory activity against PI3K alpha and mTOR kinase. Its introduction of the arylurea group improved the cellular and kinase activities of the target compounds. Additionally, it demonstrated low toxicity and good safety in toxicity and hemolysis experiments.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xin Sun, Binliang Zhang, Leixuan Luo, Yang Yang, Bin He, Qian Zhang, Linxiao Wang, Shan Xu, Pengwu Zheng, Wufu Zhu
Summary: A series of novel compounds were synthesized and evaluated in this study, and it was found that the compound XIN-9 exhibited potent inhibition against PI3K and mTOR. The results indicate that XIN-9 has potential as an anticancer agent by blocking the growth and survival of cancer cells.
BIOORGANIC CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Jianzhang Yang, Yu Chang, Jean Ching-Yi Tien, Zhen Wang, Yang Zhou, Pujuan Zhang, Weixue Huang, Josh Vo, Ingrid J. Apel, Cynthia Wang, Victoria Zhixuan Zeng, Yunhui Cheng, George Xiaoju Wang, Arul M. Chinnaiyan, Ke Ding
Summary: In this study, highly potent and selective dual CDK12/13 degraders were discovered using the PROTAC technology. The optimal compound 7f effectively degraded CDK12 and CDK13, and inhibited the proliferation of TNBC cell lines.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Haotian Gao, Zaolin Li, Kai Wang, Yuhan Zhang, Tong Wang, Fang Wang, Youjun Xu
Summary: A series of sulfonamide methoxypyridine derivatives were synthesized as novel potent PI3K/mTOR dual inhibitors, and compound 22c showed strong inhibitory activity and promising characteristics in cell cycle, apoptosis, and AKT phosphorylation. Hence, 22c is a promising candidate for further research and exploration.