机构：[1]School of Pharmaceutical Sciences, China.[2]Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, China, 510006.[3]Shanghai Institute for Advanced Immunochemical Studies, Shanghai Tech University, Shanghai, China, 201210.[4]International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, China.深圳市中医院深圳医学信息中心[5]Department of Laboratory Medicine, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China, 510317.[6]State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-Sen University, Guangzhou, China, 510006.[7]Department of Structural Biology, Stanford University, Stanford, CA, USA, 95305.[8]MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275.
Overexpression of AKR1C3, an aldo-keto reductase, was recently discovered in liver cancers. In this study, an inverse correlation between AKR1C3 expression and liver cancer patient survival was observed. AKR1C3 inhibitors, however, failed to suppress liver cancer cell growth. The prodrug TH3424, which releases a DNA alkylating reagent upon reduction by AKR1C3, was developed to target tumors with overexpression of AKR1C3. TH3424 showed specific killing of liver cancer cells with AKR1C3 overexpression both in vitro and in vivo. In patient-derived mouse xenograft models, TH3424 at doses as low as 1.5 mg/kg eliminated liver tumors with no apparent toxicity. Conclusion: TH3424 is a promising drug candidate for liver cancer and other types of cancers overexpressing AKR1C3.
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基金：
We appreciate the Innovative R&D Team Leadership Program of Guangdong Province (PR China)
(2011Y038) (P. H., C. W., Y. W., C. W., C. Z., D. C., J. L., R. D. K., W. X., Q. L., and Z. W.) for the
financial support of this work.
第一作者机构：[1]School of Pharmaceutical Sciences, China.[2]Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, China, 510006.
共同第一作者：
通讯作者：
通讯机构：[1]School of Pharmaceutical Sciences, China.[2]Centre for Cellular & Structural Biology, Sun Yat-Sen University, Guangzhou, China, 510006.[7]Department of Structural Biology, Stanford University, Stanford, CA, USA, 95305.[8]MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China, 510275.[*1]Department of Structural Biology, Stanford University, 299 Campus Drive West, Stanford, CA, USA, 95305[*2]MOE Key Laboratory of Gene Function and Regulation, School of Life Sciences, Sun Yat-Sen University, No. 135 Xingang West Road,Guangzhou, China, 510275[*3]School of Pharmaceutical Sciences, Sun YatSen University, No.132, East Outer Ring Road, Guangzhou, China, 510006
推荐引用方式(GB/T 7714)：
He Ping,Wang Chunnian,Wang Yanlan,et al.A novel AKR1C3 specific prodrug TH3424 with potent anti-tumor activity in liver cancer.[J].CLINICAL PHARMACOLOGY & THERAPEUTICS.2021,110(1):229-237.doi:10.1002/cpt.2171.
APA：
He Ping,Wang Chunnian,Wang Yanlan,Wang Caiyan,Zhou Changhua...&Wang Zhong.(2021).A novel AKR1C3 specific prodrug TH3424 with potent anti-tumor activity in liver cancer..CLINICAL PHARMACOLOGY & THERAPEUTICS,110,(1)
MLA：
He Ping,et al."A novel AKR1C3 specific prodrug TH3424 with potent anti-tumor activity in liver cancer.".CLINICAL PHARMACOLOGY & THERAPEUTICS 110..1(2021):229-237
医学