Selection of Small Molecules that Bind to and Activate the Insulin Receptor from a DNA-Encoded Library of Natural Products

Xie, Jia; Wang, Shuyue; Ma, Peixiang; Ma, Fei; Li, Jie; Wang, Wei; Lu, Fengping; Xiong, Huan; Gu, Yuang; Zhang, Shuning; Xu, Hongtao; Yang, Guang; Lerner, Richard A.

doi:10.1016/j.isci.2020.101197

Cited by 39 publications

(30 citation statements)

References 68 publications

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“…Therefore, further elucidating the relationships of pharmacological mechanisms of bioactive constituents are still required. Gratefully, an emerging technology, DNA-encoded library (DEL) and especially the natural product DNA-encoded library ( n DEL) has already showed their potential in identification of protein targets of natural products, thus could be used to handle this issue ( Ma et al, 2019 ; Xie et al, 2020 ). Compounds that isolated from K. galanga could be efficiently annotated with unique DNA tags by using the n DEL technology to form a K. galanga focused n DEL.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Wang

Zhao

et al. 2021

Front. Pharmacol.

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K. galanga is an aromatic medicinal herb. It is locally to India and distributed in China, Myanmar, Indonesia, Malaysia, and Thailand. K. galanga is a Traditional Chinese Herb Medicine (TCHM), which has been applied to treat cold, dry cough, toothaches, rheumatism, hypertension and so on. In addition, it has been used widely as spices since its highly aromas. The aim of this review is to compile and update the current progresses of ethnomedicinal uses, phytochemistry, pharmacology and toxicology of K. galanga. All the data on K. galanga were based on different classical literary works, multiple electronic databases including SciFinder, Web of Science, PubMed, etc. The results showed that ninety-seven compounds have been identified from rhizome of K. galanga, including terpenoids, phenolics, cyclic dipeptides, flavonoids, diarylheptanoids, fatty acids and esters. Modern pharmacology studies revealed that extracts or secondary metabolites of the herb possessed anti-inflammatory, anti-oxidant, anti-tumorous, anti-bacterial, and anti-angiogenesis effects, which were closely related to its abundant ethnomedicinal uses. In conclusion, although previous research works have provided various information of K. galanga, more in-depth studies are still necessary to systemically evaluate phytochemistry, pharmacological activities, toxicity and quality control of this herb.

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Section: Conclusion and Perspectivementioning

confidence: 99%

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Wang

Zhao

et al. 2021

Front. Pharmacol.

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“… 4) Beyond CuAAC click chemistry, which generates 1,2,3-triazole derivatives, some other emerging click chemistries like SuFEX chemistry have already shown their power in the generation of valuable hit molecules, and thus also could be used in natural product modification in the future. 5) Notably, another powerful hit screening technology DNA-encoded library (DEL), and especially the natural product DNA-encoded library ( n DEL), have already shown their power in the screening of some challenge protein targets ( Ma et al, 2019 ; Xie et al, 2020 ). So, if we can connect natural products with DNA-encoded libraries and diversify them by click chemistry, we could quickly generate a huge natural product derivative library with unprecedented skeleton diversity.…”

Section: Conclusion Remarks and Future Perspectivesmentioning

confidence: 99%

“…5) Notably, another powerful hit screening technology DNA-encoded library (DEL), and especially the natural product DNA-encoded library ( n DEL), have already shown their power in the screening of some challenge protein targets ( Ma et al, 2019 ; Xie et al, 2020 ). So, if we can connect natural products with DNA-encoded libraries and diversify them by click chemistry, we could quickly generate a huge natural product derivative library with unprecedented skeleton diversity.…”

Section: Conclusion Remarks and Future Perspectivesmentioning

confidence: 99%

“…Natural product-based drug discovery can date back to the isolation of morphine, the first pharmacologically active pure natural product which was purified by Friedrich Sertürner more than 200 years ago. From then on, considerable works have been devoted to the synthesis of natural derivatives ( Wang M. et al, 2018 ; Foley et al, 2020 ), and/or natural product-like screening libraries with the aim of therapeutic drug discovery ( Huigens et al, 2013 ; Crane and Gademann, 2016 ; Ma et al, 2019 ; Wilson et al, 2020 ; Xie et al, 2020 ). These efforts have led to the discovery of various important clinical drugs, such as anticancer agents (e.g., taxol and doxorubicin), immunosuppressants (e.g., cyclosporine and doxorubicin), antimalarial agents (e.g., quinine and artemisinin) and lipid regulate drugs (e.g., lovastatin and relatives).…”

Section: Introductionmentioning

confidence: 99%

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Click Chemistry in Natural Product Modification

Zhang

Zhao

et al. 2021

Front. Chem.

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Click chemistry is perhaps the most powerful synthetic toolbox that can efficiently access the molecular diversity and unique functions of complex natural products up to now. It enables the ready synthesis of diverse sets of natural product derivatives either for the optimization of their drawbacks or for the construction of natural product-like drug screening libraries. This paper showcases the state-of-the-art development of click chemistry in natural product modification and summarizes the pharmacological activities of the active derivatives as well as the mechanism of action. The aim of this paper is to gain a deep understanding of the fruitful achievements and to provide perspectives, trends, and directions regarding further research in natural product medicinal chemistry.

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“…Therefore, insulin replacement therapy is widely used to treat patients with T1DM and some patients with T2DM. However, many reports suggested that recombinant insulin, its analogues and insulin mimetic can be used to treat patients with diabetes ( Babu et al., 2020 ; Moura et al., 2020 ; Qiang et al., 2014 ; Xie et al., 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism

Saetan

Wonglapsuwan

Chotigeat

2020

Heliyon

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The number of patients with insulin-resistant diabetes has significantly increased. Thus, alternative insulin mimetics are required for such patients. Some evidences indicate that ribosomal protein L10a (RpL10a) is involved in the insulin pathway. In addition, we previously demonstrated that recombinant RpL10a from Fenneropenaeus merguiensis ( Fm -RpL10a) could stimulate cell proliferation and trehalose metabolism in RpL10a–over-expressing flies by inducing insulin receptor ( InR ) expression and some insulin signaling mediators phosphorylation. In this study, we investigated the in silico binding between Fm -RpL10a and InR. The results indicated that Fm -RpL10a bound to InR at residues 635–640 and 697–702 of the FnIII2 domain. This binding was confirmed using a pull-down and immunofluorescence assay. Further analysis indicated that Fm -RpL10a could stimulate glucose utilisation by insulin-resistant cells (IRCs) and healthy cells. Additionally, Fm -RpL10a at a low concentration (1 μg/ml) altered some glucose metabolism-related genes expression in Fm -RpL10a treated IRCs. The qRT-PCR result revealed the up-regulation of Hk1 , which encode key enzymes in glycolysis. Conversely, the expression of G6pc3 , which participates in gluconeogenesis, was down-regulated. Overall, the results suggest that Fm -RpL10a can alleviate insulin resistance by stimulating insulin signaling via the FnIII2 domain of InR and activate glycolysis. Therefore, Fm -RpL10a may be a candidate insulin mimetic for the treatment of diabetes.

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Selection of Small Molecules that Bind to and Activate the Insulin Receptor from a DNA-Encoded Library of Natural Products

Cited by 39 publications

References 68 publications

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Kaempferia galanga L.: Progresses in Phytochemistry, Pharmacology, Toxicology and Ethnomedicinal Uses

Click Chemistry in Natural Product Modification

Effect of the interaction between ribosomal protein L10a and insulin receptor on carbohydrate metabolism

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