PROTAC: A Novel Technology for Drug Development**

Li, Jie; Liu, Jie‐Qing

doi:10.1002/slct.202003162

Cited by 5 publications

(3 citation statements)

References 155 publications

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“…By selectively degrading target proteins, it can more effectively inhibit the growth and metastasis of tumor cells and overcome drug resistance. Although there are still some challenges, the continuous development and optimization of PROTAC technology is expected to achieve its application in the clinic [14].…”

Section: Reducing Side Effectsmentioning

confidence: 99%

Application of PROTACs in the Pharmaceutical Direction

Zhou¹,

Zhang²,

Liu³

2023

IJBLS

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Proteolysis targeting chimeras (PROTACs) technology is a novel drug development strategy that can treat diseases by selectively degrading targeted proteins. PROTACs consist of two molecules, one of which binds to the target protein while the other binds to the protein degradation enzyme, thus promoting the degradation of the target protein. Compared to the mechanism of action of traditional drugs, PROTAC technology has many advantages, such as high selectivity, reversibility, and low dosage effects. PROTAC technology has been widely applied in multiple fields, especially in cancer research. PROTACs can target cancer-related proteins for degradation, thereby inhibiting tumor growth and metastasis. For instance, PROTACs targeting proteins such as BCL-2 and BRD4 have been extensively researched and applied in cancer treatment. In addition, PROTAC technology can also be applied to multiple fields such as neurodegenerative diseases, immunotherapy, metabolic diseases, and infectious diseases. Although PROTAC technology has broad application prospects, there are still some challenges, such as how to improve the stability and pharmacokinetics of PROTACs, and how to prepare large-scale PROTACs. Therefore, further research and optimization are still needed to further improve PROTAC technology and promote its application in clinical treatment.

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Section: Reducing Side Effectsmentioning

confidence: 99%

Application of PROTACs in the Pharmaceutical Direction

Zhou¹,

Zhang²,

Liu³

2023

IJBLS

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“…Three key applications that can all be considered as linker design are scaffold hopping, 9,10 fragment linking, 11,12 and PROTAC design. 13,14 Examples of these design tasks are shown in Fig. 1a-c.…”

Section: Introductionmentioning

confidence: 99%

Deep generative design with 3D pharmacophoric constraints

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Deep Generative Design with 3D Pharmacophoric Constraints

Imrie

Hadfield

Bradley

et al. 2021

Preprint

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Generative models have increasingly been proposed as a solution to the molecular design problem. However, it has proved challenging to control the design process or incorporate prior knowledge, limiting their practical use in drug discovery. In particular, generative methods have made limited use of three-dimensional (3D) structural information even though this is critical to binding. This work describes a method to incorporate such information and demonstrates the benefit of doing so. We combine an existing graph-based deep generative model, DeLinker, with a convolutional neural network to utilise physically-meaningful 3D representations of molecules and target pharmacophores. We apply our model, DEVELOP, to both linker and R-group design, demonstrating its suitability for both hit-to-lead and lead optimisation. The 3D pharmacophoric information results in improved generation and allows greater control of the design process. In multiple large-scale evaluations, we show that including 3D pharmacophoric constraints results in substantial improvements in the quality of generated molecules. On a challenging test set derived from PDBbind, our model improves the proportion of generated molecules with high 3D similarity to the original molecule by over 300%. In addition, DEVELOP recovers 10x more of the original molecules compared to the baseline DeLinker method. Our approach is general-purpose, readily modifiable to alternate 3D representations, and can be incorporated into other generative frameworks. Code is available at https://github.com/oxpig/DEVELOP.

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PROTAC: A Novel Technology for Drug Development**

Cited by 5 publications

References 155 publications

Application of PROTACs in the Pharmaceutical Direction

Application of PROTACs in the Pharmaceutical Direction

Deep generative design with 3D pharmacophoric constraints

Deep Generative Design with 3D Pharmacophoric Constraints

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