Drugging the 'undruggable' cancer targets
TLDR
Four scientists working in the 'undruggable' cancer research field are asked for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.Abstract:
The term 'undruggable' was coined to describe proteins that could not be targeted pharmacologically. However, progress is being made to 'drug' many of these targets, and therefore more appropriate terms might be 'difficult to drug' or 'yet to be drugged'. Many desirable targets in cancer fall into this category, including the RAS and MYC oncogenes, and pharmacologically targeting these intractable proteins is now a key challenge in cancer research that requires innovation and the development of new technologies. In this Viewpoint article, we asked four scientists working in this field for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of research.read more
Citations
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Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics
Yunxia Wang,Song Zhang,Fengcheng Li,Ying Zhou,Ying Zhang,Zhengwen Wang,Runyuan Zhang,Jiang Zhu,Yuxiang Ren,Ying Tan,Chu Qin,Yinghong Li,Xiaoxu Li,Yu Zong Chen,Feng Zhu +14 more
TL;DR: The Therapeutic Target Database (TTD) is constructed with expanded information about target-regulating microRNAs and transcription factors, target-interacting proteins, and patented agents and their targets, which can be conveniently retrieved and is further enriched with regulatory mechanisms or biochemical classes.
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A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo
Longchuan Bai,Haibin Zhou,Renqi Xu,Yujun Zhao,Krishnapriya Chinnaswamy,Donna McEachern,Jianyong Chen,Chao Yie Yang,Zhaomin Liu,Mi Wang,Liu Liu,Hui Jiang,Bo Wen,Praveen Kumar,Jennifer L. Meagher,Duxin Sun,Jeanne A. Stuckey,Shaomeng Wang +17 more
TL;DR: SD-36 achieves complete and long-lasting tumor regression in multiple xenograft mouse models at well-tolerated dose schedules and is a promising cancer therapeutic strategy.
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Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN.
Quinlan L. Sievers,Quinlan L. Sievers,Georg Petzold,Richard D. Bunker,Aline Renneville,Aline Renneville,Mikolaj Slabicki,Mikolaj Slabicki,Mikolaj Slabicki,Brian J. Liddicoat,Brian J. Liddicoat,Wassim Abdulrahman,Tarjei S. Mikkelsen,Benjamin L. Ebert,Benjamin L. Ebert,Benjamin L. Ebert,Nicolas H. Thomä +16 more
TL;DR: The human ZF “degrome” is defined in the context of thalidomide, lenalidomid, and pomalidomides to characterize the ZF-drug-CRBN interaction structurally and functionally and determine whether different thalidmide analogs degrade distinct ZFs.
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The role of ubiquitination in tumorigenesis and targeted drug discovery
TL;DR: The latest progress in understanding the substrates for ubiquitination and their special functions in tumor metabolism regulation, TME modulation and CSC stemness maintenance are summarized and potential therapeutic targets for cancer are reviewed.
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Selective degradation of splicing factor CAPERα by anticancer sulfonamides
Taisuke Uehara,Yukinori Minoshima,Koji Sagane,Naoko Hata Sugi,Kaoru Mitsuhashi,Noboru Yamamoto,Hiroshi Kamiyama,Kentaro Takahashi,Yoshihiko Kotake,Mai Uesugi,Akira Yokoi,Atsushi Inoue,Taku Yoshida,Miyuki Mabuchi,Akito Tanaka,Takashi Owa +15 more
TL;DR: These sulfonamides represent selective chemical probes for disrupting CAPERα function and designate DCAFs as promising drug targets for promoting selective protein degradation in cancer therapy.
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