DNA-encoded libraries (DELs): a review of on-DNA chemistries and their output

Shi, Ying; Wu, Yan-ran; Yu, Jianqiang; Zhang, Wannian; Zhuang, Chunlin

doi:10.1039/d0ra09889b

Cited by 84 publications

(71 citation statements)

References 119 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many organic synthetic methods are excluded from the synthesis of DECL because the reaction conditions are incompatible with DNA. The newly reported DNA‐compatible reactions are expanding the usability of DNA‐encoding, 50 , 51 , 52 , 53 , 54 , 55 and machine learning can help to identify hits by analyzing the screening results. 56 …”

Section: Discussionmentioning

confidence: 99%

Combinatorial technology revitalized by DNA‐encoding

Furka

2021

MedComm

View full text Add to dashboard Cite

Combinatorial chemistry invented nearly 40 years ago was welcomed with enthusiasm in the drug research community. The method offered access to a practically unlimited number of new compounds. The new compounds however are mixtures, and methods had to be developed for the identification of the bioactive components. This was one of the reasons why the method could not providethe expected cornucopia of new drugs. Among the different screening methods, two approaches seem to offer the best results. One of them is based on the intrinsic property of the combinatorial split and pool solid‐phase synthesis: One compound forms on each bead of the solid support. Different methods have been developed to encode the beads and identify the structure of compounds formed on them. The most important method applies DNA oligomers for encoding. As a second approach in screening, DNA‐encoded combinatorial libraries are synthesized omitting the solid support and the mixtures are screened in solution using affinity binding methods. Libraries containing billions and even trillions of components are synthesized and successfully tested, which led to the identification of a significant number of new leads.

show abstract

Section: Discussionmentioning

confidence: 99%

Combinatorial technology revitalized by DNA‐encoding

Furka

2021

MedComm

View full text Add to dashboard Cite

show abstract

“…individual DNA with unique comprehensive information on each library member. 388,389 This approach is increasingly being utilized by primary pharmaceutical companies in multiple drug discovery procedures for hit and lead generation. The DEL technology can thrift the cost of time, fund, and storage space necessary for the discovery of target compounds, and enable prospecting of chemical spaces with much higher orders of magnitude than traditional HTS approaches, which is beneficial in the early stage of drug discovery.…”

Section: Allosteric Methodsmentioning

confidence: 99%

“…THE DNA‐encoded library (DEL) approach applies abundant libraries of small molecules that are covalently linked to individual DNA with unique comprehensive information on each library member 388,389 . This approach is increasingly being utilized by primary pharmaceutical companies in multiple drug discovery procedures for hit and lead generation.…”

Section: Emerging Solutionsmentioning

confidence: 99%

Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

Pei

Guo

Peng

et al. 2022

Medicinal Research Reviews

View full text Add to dashboard Cite

The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor‐associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA‐binding of transcriptional factors, and inhibition of the protein–protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.

show abstract

“…This is followed by several split and pool cycles of chemistry to synthesize and simultaneously encode additional units (Scheme 1). 8,9 Upon library completion, the generated structures are incubated against an immobilized target protein, after which the low-affinity or non-binding ligands are washed away. 10,11 The DNA barcode of the remaining high-affinity ligands are then amplified using polymerase chain reaction (PCR), and the corresponding chemical identities can be decoded through next generation sequencing of the DNA barcode.…”

Section: Introductionmentioning

confidence: 99%