北京大学曾慧慧抗癌新药多篇文章严重造假

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北京大学曾慧慧抗癌新药多篇文章严重造假

从选择一个靶点，到形成潜在的新药候选分子，这个过程需要多长的时间？过去的回答可能是数月，乃至数年。但在近日，来自人工智能药物发现公司Insilico Medicine、药明康德以及多伦多大学的科学家们在《自然》子刊 Nature Biotechnology 上给出了不同的答案。他们用一种称为生成张力强化学习（GENTRL）的新 AI 系统，将这一数字缩短到了仅仅 21 天。

国家一类抗癌新药乙烷硒啉进入一期临床研究阶段

此为来源于中新网2009年04月09日的报道。由甘肃奇正藏药有限公司与北京大学共同开发研制的国家一类抗癌新药乙烷硒啉，该药的研发取得标志性进展，目前进入一期临床研究。根据国家食品药品监督管理局临床试验要求，在临床一期试验期间，将进行人体耐受、人体药代动力学和药效学等试验。据了解，近年来中国一类新药进入一期临床试验的只有少数几个。据悉，在经药效学、药理学、毒理学试验研究后表明，乙烷硒啉是硫氧还蛋白还原酶抑制剂，它在抑制硫氧还蛋白还原酶同时，表现出具有抗肿瘤转移、抑制肿瘤生长、消退已形成肿瘤，并在与其它药物联用时，有协同杀伤肿瘤细胞的功效。甘肃省科技厅农村与社会发展处透露消息称，目前正在进行临床试验的乙烷硒啉片剂拟用于肿瘤治疗，首选消化道肿瘤和肺癌等临床适应症，并侧重其中的腺癌类，对结肠癌、胃癌、肝癌、肺癌中的非小细胞肺癌、高转肺癌和高转移腺癌等多种肿瘤有抑制作用。据悉，乙烷硒啉属抗肿瘤类创新型靶向给药的化学合成药，现在已经取得了国家食品药品监督管理局的临床批件，正在按要求进行Ⅰ期临床研究(乙烷硒啉(原料药)。该药为化学创新药物，属原始创新品种，在该药的临床前研究期间，已申请多项国内外发明专利，拥有独立的知识产权。

十多年过去了，此药的消息再无任何二期临床试验的任何报道。一期临床试验效果如何呢？2014年《广西医科大学》陆开智“乙烷硒啉的临床药代动力学研究”， 结果表明,受试者口服乙烷硒啉分散片后,乙烷硒啉在体内迅速代谢,血浆和尿液中均未发现乙烷硒啉原形药物。

笔者饶有兴趣搜索了乙烷硒啉的研发者北京大学药学院曾慧慧教授的文章，不看不知道，一看吓一跳，美国Elisabeth M Bik博士在pubpeer列出了曾慧慧的3篇文章严重造假，3篇恰好都是有关乙烷硒啉的。曾慧慧竟然无言以对，不敢回复质疑。

https://pubpeer.com/search?q=Huihui+Zeng

https://pubpeer.com/publications/3C2B1FB36EBCA94AFC368007DF6452#

Butaselen prevents hepatocarcinogenesis and progression through inhibiting thioredoxin reductase activity

Redox Biology (2018) - 1 Comment　　pubmed: 28965082 doi: 10.1016/j.redox.2017.09.014 issn: 2213-2317

Xiaoqing Zheng , Weiwei Ma , Ruoxuan Sun , Hanwei Yin , Fei Lin , Yuxi Liu , Wei Xu , Huihui Zeng

State Key Laboratory of Natural and Biomimetic Drugs, No. 38, Xueyuan Road, Beijing 100191, PR China…　　#1 Elisabeth M Bik commented 21 days ago

Figure 3.

· Red boxes: Lanes 2-5 of the pNF-kB p65 blot in Figure 3D look unexpectedly similar to lanes 2-5 of the IL-6 blot in Figure 3F. Of note, the first lanes look very different, and the panels represent different proteins.

The antimetastatic effect and underlying mechanisms of thioredoxin reductase inhibitor ethaselen

Free Radical Biology and Medicine (2019) - 4 Comments　　doi: 10.1016/j.freeradbiomed.2018.11.030 issn: 0891-5849 pubmed: 30496814 issn: 1873-4596

Xiaoqing Zheng , Yifan Chen , Man Bai , Yuxi Liu , Binyuan Xu , Ruoxuan Sun , Huihui Zeng

State Key Laboratory of Natural and Biomimetic Drugs, Peking University, No. 38, Xueyuan Road, Beiji…

#1 Elisabeth M Bik commented 21 days ago

Figure 1C.

· Blue boxes: The 0h/0 uM BBSKE panel and the 0h/2 uM BBSKE panel look unexpectedly similar. Could the authors please check?

#2 Elisabeth M Bik commented 21 days ago

Figure 4D.

· Green boxes. The"None" E-cadherin and DAPI panels look similar to the “BBSKE 8 uM” E-cadherin and DAPI panels. The “Merge” panels look different, suggesting something might have gone wrong during figure assembly. Could the authors please check?

#3 Elisabeth M Bik commented 21 days ago

Figure 4E.

· Orange boxes. The EGFR panels representing MCF-7 and LoVo cells appear to look very similar.

#4 Elisabeth M Bik commented 21 days ago

Additional findings in Figure 1C and 5B.

· Pink boxes: In the MCF-7 cells at 24h, the “0 uM BBSKE” and the “8 uM BBSKE” panels look unexpectedly similar to each other.

· Blue boxes: For the LoVo cells at 0h, the"0 uM BBSKE" and the “2 uM BBSKE” panels of Figure 1C not only look similar to each other as pointed out in comment #1, they also look similar to the 0h “shNC” panel in Figure 5B. Could the authors please clarify if the negative control for a lentiviral shRNA transduction would not just be an empty, untransfected cell, but a cell transfected with an empty vector, or scrambled RNA?

0 uM BBSKE乙烷硒啉and the “8 uM BBSKE” 乙烷硒啉 竟然完全一样，这是药物吗？

1. Publications

A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells

Journal of Zhejiang University SCIENCE B (2008) - 1 Comment　　pubmed: 18196608 doi: 10.1631/jzus.b071605 issn: 1673-1581 issn: 1862-1783

Zuo-fu Peng , Lin-xiang Lan , Fang Zhao , Jing Li , Qiang Tan , Han-wei Yin , Hui-hui Zeng

Department of Chem-Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, Ch…

#1 Elisabeth M Bik commented 19 days ago

Figure 3.

· Orange boxes: The 24h and 48h GAPDH panels in Figure 3A look similar to each other

Blue boxes: The 24h and 48h GAPDH panels in Figure 3B look similar to each other Could the authors please check?

(XYS20201109)

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