Proteolysis Targeting Chimera The Protac Technology In Drug Development Zou 2019 Cell
Proteolysis targeting chimera protac for targeted protein degradation and cancer therapy xin li1 and yongcheng song12 abstract proteolysis targeting chimera protac has been developed to be a useful technology for targeted protein degradation.
Proteolysis targeting chimera. Proteolysis targeting chimeras protacs past present and future. As the firstgeneration of proteolysistargeting chimeras have now entered clinical trials for oncology indications it is timely to consider the theoretical safety risks inherent with this modality which include off. Here we report the use of proteolysis targeting chimera protac technology to reduce the platelet toxicity of navitoclax also known as abt263 a bcl 2 and bcl xl dual inhibitor by converting. Proteolysis targeting chimera protac has been developed to be a useful technology for targeted protein degradation.
The proteolysis targeting chimera protac technology provides an attractive new approach that utilizes an event driven moa. Su s yang z gao h yang h zhu s an z et al. Here we address important milestones in the development of the protac technology as well as emphasize key. 1department of molecular cellular and developmental biology yale university new haven ct 06511 usa.
The first targeted protein degrader called proteolysis targeting chimera protac was developed about a decade ago and is currently accounting for more than 30 of the pipeline drugs. A bifunctional protac molecule consists of a ligand mostly small molecule inhibitor of the protein. A bifunctional protac molecule consists of a ligand mostly small molecule inhibitor of the protein of interest poi and a covalently linked ligand of an e3 ubiquitin ligase e3. Proteolysistargeting chimeras are a new drug modality that exploits the endogenous ubiquitin proteasome system to degrade a protein of interest for therapeutic benefit.
2 biochemie protacs bestehen aus zwei kovalent verbundenen proteinbindedomaenen. Small molecule based heterobifunctional protacs modulate protein target levels by hijacking the ubiquitin proteasome system to induce degradation of the target. Als protacs oder proteolysis targeting chimeras bezeichnet man niedermolekulare substanzen die e3 ligasen rekrutieren und dadurch den abbau von zielproteinen ausloesen. Potent and preferential degradation of cdk6 via proteolysis targeting chimera degraders.
The Protac Technology In Drug Development Zou 2019 Cell
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