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Recent progress of targeted small molecular CDK9 degraders based on PROTAC technology
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Jin-xiu LI, He-wei DONG, Wei HOU*
Acta Pharmaceutica Sinica | 2022, 57(9) : 2696 - 2708
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Acta Pharmaceutica Sinica | 2022, 57(9): 2696-2708
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Recent progress of targeted small molecular CDK9 degraders based on PROTAC technology
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Jin-xiu LI, He-wei DONG, Wei HOU*
Affiliations
  • College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
Published: 2022-09-12 doi: 10.16438/j.0513-4870.2022-0442
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CDKs proteins are a kind of cell cycle protein-dependent kinases, which serve as important roles in controlling cell division and transcriptional stages. Among them, CDK9, as a key regulator responsible for the transcriptional elongation of cells, drives the development of various malignant cells and is considered as an important target in the field of anti-tumor drug development. However, the CDK family proteins feature high conservativeness and similarity in structure, leading to the poor selectivity and severe side effects for traditional small-molecular CDK9 inhibitors, which has limited their clinical applications. In view of this, there is an urgent need to investigate CDK9 targets through a novel strategy. The PROTAC is an emerging drug discovery strategy that the degrader could specifically recognize the target protein through indirect linkage with ubiquitin ligases and ultimately eliminate the target protein through the ubiquitination degradation system. This paper provides a brief overview of the structure and function of CDK9 protein, its relationship with the poor prognosis of clinical diseases, as well as the currently reported small molecular inhibitors. The latest research progress on the targeted degradation of CDK9 protein based on PROTAC technology is highlighted. Finally, the development prospects of this target protein in this novel technology field are summarized and prospected, aiming to provide a reference for the development of antitumor drugs in this direction.

cyclin-dependent kinases 9  /  proteolysis-targeting chimera  /  inhibitor  /  antitumor  /  degradation
Jin-xiu LI, He-wei DONG, Wei HOU. Recent progress of targeted small molecular CDK9 degraders based on PROTAC technology[J]. Acta Pharmaceutica Sinica, 2022 , 57 (9) : 2696 -2708 . DOI: 10.16438/j.0513-4870.2022-0442
Year 2022 volume 57 Issue 9
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doi: 10.16438/j.0513-4870.2022-0442
  • Receive Date:2022-04-18
  • Online Date:2025-12-24
  • Published:2022-09-12
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  • Received:2022-04-18
  • Revised:2022-05-11
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    College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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