Literature DB >> 31330105

Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders.

Shang Su1, Zimo Yang2, Hongying Gao1,2, Haiyan Yang1, Songbiao Zhu3, Zixuan An1, Juanjuan Wang1, Qing Li4, Sarat Chandarlapaty4, Haiteng Deng3, Wei Wu1, Yu Rao2.   

Abstract

A focused PROTAC library hijacking cancer therapeutic target CDK6 was developed. A design principle as "match/mismatch" was proposed for understanding the degradation profile differences in these PROTACs. Notably, potent PROTACs with specific and remarkable CDK6 degradation potential were generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. The PROTAC strongly inhibited proliferation of hematopoietic cancer cells including multiple myeloma and robustly degraded copy-amplified/mutated forms of CDK6, indicating future potential clinical applications.

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Year:  2019        PMID： 31330105      PMCID： PMC6790125          DOI： 10.1021/acs.jmedchem.9b00871

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  37 in total

1.  Loss of the FAT1 Tumor Suppressor Promotes Resistance to CDK4/6 Inhibitors via the Hippo Pathway.

Authors:  Zhiqiang Li; Pedram Razavi; Qing Li; Weiyi Toy; Bo Liu; Christina Ping; Wilson Hsieh; Francisco Sanchez-Vega; David N Brown; Arnaud F Da Cruz Paula; Luc Morris; Pier Selenica; Emily Eichenberger; Ronglai Shen; Nikolaus Schultz; Neal Rosen; Maurizio Scaltriti; Edi Brogi; Jose Baselga; Jorge S Reis-Filho; Sarat Chandarlapaty
Journal:  Cancer Cell       Date:  2018-12-10       Impact factor: 31.743

2.  The Advantages of Targeted Protein Degradation Over Inhibition: An RTK Case Study.

Authors:  George M Burslem; Blake E Smith; Ashton C Lai; Saul Jaime-Figueroa; Daniel C McQuaid; Daniel P Bondeson; Momar Toure; Hanqing Dong; Yimin Qian; Jing Wang; Andrew P Crew; John Hines; Craig M Crews
Journal:  Cell Chem Biol       Date:  2017-11-09       Impact factor: 8.116

3.  Identification and Characterization of Von Hippel-Lindau-Recruiting Proteolysis Targeting Chimeras (PROTACs) of TANK-Binding Kinase 1.

Authors:  Andrew P Crew; Kanak Raina; Hanqing Dong; Yimin Qian; Jing Wang; Dominico Vigil; Yevgeniy V Serebrenik; Brian D Hamman; Alicia Morgan; Caterina Ferraro; Kam Siu; Taavi K Neklesa; James D Winkler; Kevin G Coleman; Craig M Crews
Journal:  J Med Chem       Date:  2017-07-10       Impact factor: 7.446

Review 4.  Induced protein degradation: an emerging drug discovery paradigm.

Authors:  Ashton C Lai; Craig M Crews
Journal:  Nat Rev Drug Discov       Date:  2016-11-25       Impact factor: 84.694

5.  Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition.

Authors:  Heshu Lu; Ursula Schulze-Gahmen
Journal:  J Med Chem       Date:  2006-06-29       Impact factor: 7.446

6.  Induction of apoptosis in MDA-MB-231 breast cancer cells by a PARP1-targeting PROTAC small molecule.

Authors:  Qiuye Zhao; Tianlong Lan; Shang Su; Yu Rao
Journal:  Chem Commun (Camb)       Date:  2019-01-02       Impact factor: 6.222

Review 7.  MLN4924: a novel first-in-class inhibitor of NEDD8-activating enzyme for cancer therapy.

Authors:  Steffan T Nawrocki; Patrick Griffin; Kevin R Kelly; Jennifer S Carew
Journal:  Expert Opin Investig Drugs       Date:  2012-07-16       Impact factor: 6.206

Review 8.  Targeting CDK4 and CDK6: From Discovery to Therapy.

Authors:  Charles J Sherr; David Beach; Geoffrey I Shapiro
Journal:  Cancer Discov       Date:  2015-12-11       Impact factor: 39.397

9.  Acquired CDK6 amplification promotes breast cancer resistance to CDK4/6 inhibitors and loss of ER signaling and dependence.

Authors:  C Yang; Z Li; T Bhatt; M Dickler; D Giri; M Scaltriti; J Baselga; N Rosen; S Chandarlapaty
Journal:  Oncogene       Date:  2016-10-17       Impact factor: 9.867

10.  The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is a versatile combination partner in preclinical cancer models.

Authors:  Sunkyu Kim; Ralph Tiedt; Alice Loo; Thomas Horn; Scott Delach; Steven Kovats; Kristy Haas; Barbara Schacher Engstler; Alexander Cao; Maria Pinzon-Ortiz; Iain Mulford; Michael G Acker; Rajiv Chopra; Christopher Brain; Emmanuelle di Tomaso; William R Sellers; Giordano Caponigro
Journal:  Oncotarget       Date:  2018-10-16
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  41 in total

Review 1.  PROTACs: great opportunities for academia and industry.

Authors:  Xiuyun Sun; Hongying Gao; Yiqing Yang; Ming He; Yue Wu; Yugang Song; Yan Tong; Yu Rao
Journal:  Signal Transduct Target Ther       Date:  2019-12-24

2.  A NSD3-targeted PROTAC suppresses NSD3 and cMyc oncogenic nodes in cancer cells.

Authors:  Chenxi Xu; Fanye Meng; Kwang-Su Park; Aaron J Storey; Weida Gong; Yi-Hsuan Tsai; Elisa Gibson; Stephanie D Byrum; Dongxu Li; Rick D Edmondson; Samuel G Mackintosh; Masoud Vedadi; Ling Cai; Alan J Tackett; H Ümit Kaniskan; Jian Jin; Gang Greg Wang
Journal:  Cell Chem Biol       Date:  2021-08-31       Impact factor: 8.116

Review 3.  Glioblastoma: Current Status, Emerging Targets, and Recent Advances.

Authors:  Amandeep Thakur; Chetna Faujdar; Ram Sharma; Sachin Sharma; Basant Malik; Kunal Nepali; Jing Ping Liou
Journal:  J Med Chem       Date:  2022-07-05       Impact factor: 8.039

Review 4.  Critical Assessment of Targeted Protein Degradation as a Research Tool and Pharmacological Modality.

Authors:  Milka Kostic; Lyn H Jones
Journal:  Trends Pharmacol Sci       Date:  2020-03-26       Impact factor: 14.819

5.  Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders.

Authors:  Yudao Shen; Guozhen Gao; Xufen Yu; Huensuk Kim; Li Wang; Ling Xie; Megan Schwarz; Xian Chen; Ernesto Guccione; Jing Liu; Mark T Bedford; Jian Jin
Journal:  J Med Chem       Date:  2020-08-21       Impact factor: 7.446

6.  Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.

Authors:  Liguo Wang; Xuejing Shao; Tianbai Zhong; Yue Wu; Aixiao Xu; Xiuyun Sun; Hongying Gao; Yongbo Liu; Tianlong Lan; Yan Tong; Xue Tao; Wenxin Du; Wei Wang; Yingqian Chen; Ting Li; Xianbin Meng; Haiteng Deng; Bo Yang; Qiaojun He; Meidan Ying; Yu Rao
Journal:  Nat Chem Biol       Date:  2021-03-04       Impact factor: 15.040

Review 7.  Cell cycle on the crossroad of tumorigenesis and cancer therapy.

Authors:  Jing Liu; Yunhua Peng; Wenyi Wei
Journal:  Trends Cell Biol       Date:  2021-07-22       Impact factor: 20.808

Review 8.  E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points.

Authors:  Aleša Bricelj; Christian Steinebach; Robert Kuchta; Michael Gütschow; Izidor Sosič
Journal:  Front Chem       Date:  2021-07-05       Impact factor: 5.221

Review 9.  Targeting Protein Kinases Degradation by PROTACs.

Authors:  Fei Yu; Ming Cai; Liang Shao; Jihong Zhang
Journal:  Front Chem       Date:  2021-06-30       Impact factor: 5.221

Review 10.  Opportunities and Challenges of Small Molecule Induced Targeted Protein Degradation.

Authors:  Ming He; Wenxing Lv; Yu Rao
Journal:  Front Cell Dev Biol       Date:  2021-06-22
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