In silico identification of natural product inhibitors of JAK2

Hai Jing Zhong; Sheng Lin; I. Lam Tam; Lihua Lu; Daniel Shiu Hin Chan; Edmond Dik Lung MA; Chung Hang Leung

doi:10.1016/j.ymeth.2014.07.003

In silico identification of natural product inhibitors of JAK2

Hai Jing Zhong, Sheng Lin, I. Lam Tam, Lihua Lu, Daniel Shiu Hin Chan, Edmond Dik Lung MA^*, Chung Hang Leung

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

8 Citations (Scopus)

Abstract

Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.

Original language	English
Pages (from-to)	21-25
Number of pages	5
Journal	Methods
Volume	71
Issue number	C
DOIs	https://doi.org/10.1016/j.ymeth.2014.07.003
Publication status	Published - 2015

Scopus Subject Areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

6-Chloroemodic acid
Emodic acid
JAK2
Natural product
Virtual screening

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10.1016/j.ymeth.2014.07.003

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title = "In silico identification of natural product inhibitors of JAK2",

abstract = "Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.",

keywords = "6-Chloroemodic acid, Emodic acid, JAK2, Natural product, Virtual screening",

author = "Zhong, {Hai Jing} and Sheng Lin and Tam, {I. Lam} and Lihua Lu and Chan, {Daniel Shiu Hin} and MA, {Edmond Dik Lung} and Leung, {Chung Hang}",

note = "Funding Information: This work is supported by Hong Kong Baptist University ( FRG2/12-13/021 and FRG2/13-14/008 ), Centre for Cancer and Inflammation Research , School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund ( HMRF/13121482 , HMRF/11101212 ), the Research Grants Council ( HKBU/201811 , HKBU/204612 , and HKBU/201913 ), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12), the Science and Technology Development Fund , Macao SAR (103/2012/A3) and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG121(Y3-L2)-ICMS12-LCH and MRG023/LCH/2013/ICMS). ",

year = "2015",

doi = "10.1016/j.ymeth.2014.07.003",

language = "English",

volume = "71",

pages = "21--25",

journal = "Methods",

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T1 - In silico identification of natural product inhibitors of JAK2

AU - Zhong, Hai Jing

AU - Lin, Sheng

AU - Tam, I. Lam

AU - Lu, Lihua

AU - Chan, Daniel Shiu Hin

AU - MA, Edmond Dik Lung

AU - Leung, Chung Hang

N1 - Funding Information: This work is supported by Hong Kong Baptist University ( FRG2/12-13/021 and FRG2/13-14/008 ), Centre for Cancer and Inflammation Research , School of Chinese Medicine (CCIR-SCM, HKBU), the Health and Medical Research Fund ( HMRF/13121482 , HMRF/11101212 ), the Research Grants Council ( HKBU/201811 , HKBU/204612 , and HKBU/201913 ), the French National Research Agency/Research Grants Council Joint Research Scheme (A-HKBU201/12), the Science and Technology Development Fund , Macao SAR (103/2012/A3) and the University of Macau (MYRG091(Y3-L2)-ICMS12-LCH, MYRG121(Y3-L2)-ICMS12-LCH and MRG023/LCH/2013/ICMS).

PY - 2015

Y1 - 2015

N2 - Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.

AB - Emodic acid (1) and 6-chloroemodic acid (2) have been identified from a natural product database as useful scaffolds for the future development of novel JAK2 inhibitors using structure-based high-throughput virtual screening. Low-energy binding conformations of 1 and 2 in the JAK2 PTK domain were generated by virtual ligand docking and were found to overlap considerably with the binding pose of CMP6, a known JAK2 inhibitor. Compounds 1 and 2 displayed low micromolar efficacies against JAK2 enzyme activity and JAK2 autophosphorylation in human erythroleukemia cells, and inhibited STAT3 DNA-binding activity in a human hepatocarcinoma cell line.

KW - 6-Chloroemodic acid

KW - Emodic acid

KW - JAK2

KW - Natural product

KW - Virtual screening

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JO - Methods

JF - Methods

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In silico identification of natural product inhibitors of JAK2

Abstract

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