Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Dehydrocrenatidine Is a Novel Janus Kinase Inhibitor

Jing Zhang, Ning Zhu, Yuping Du, Qifeng Bai, Xing Chen, Jing Nan, Xiaodong Qin, Xinxin Zhang, Jianwen Hou, Qin Wang and Jinbo Yang
Molecular Pharmacology April 2015, 87 (4) 572-581; DOI: https://doi.org/10.1124/mol.114.095208
Jing Zhang
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ning Zhu
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuping Du
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qifeng Bai
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xing Chen
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jing Nan
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaodong Qin
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xinxin Zhang
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jianwen Hou
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qin Wang
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jinbo Yang
Schools of Life Sciences and Basic Medical Sciences, Lanzhou University, Lanzhou, China
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF
Loading

Abstract

Janus kinase (JAK) 2 plays a pivotal role in the tumorigenesis of signal transducers and activators of transcription (STAT) 3 constitutively activated solid tumors. JAK2 mutations are involved in the pathogenesis of various types of hematopoietic disorders, such as myeloproliferative disorders, polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Thus, small-molecular inhibitors targeting JAK2 are potent for therapy of these diseases. In this study, we screened 1,062,608 drug-like molecules from the ZINC database and 2080 natural product chemicals. We identified a novel JAK family kinase inhibitor, dehydrocrenatidine, that inhibits JAK-STAT3–dependent DU145 and MDA-MB-468 cell survival and induces cell apoptosis. Dehydrocrenatidine represses constitutively activated JAK2 and STAT3, as well as interleukin-6–, interferon-α−, and interferon-γ–stimulated JAK activity, and STAT phosphorylation, and suppresses STAT3 and STAT1 downstream gene expression. Dehydrocrenatidine inhibits JAKs-JH1 domain overexpression–induced STAT3 and STAT1 phosphorylation. In addition, dehydrocrenatidine inhibits JAK2-JH1 kinase activity in vitro. Importantly, dehydrocrenatidine does not show significant effect on Src overexpression and epidermal growth factor–induced STAT3 activation. Our results indicate that dehydrocrenatidine is a JAK-specific inhibitor.

Footnotes

    • Received August 3, 2014.
    • Accepted January 12, 2015.
  • J.Z. and N.Z. contributed equally to this work.

  • This work was supported by the Science and Technology Support Project of Gansu Providence [Grant 1104FK CA123]; the Ministry of Science and Technology of the People’s Republic of China [Grant 2009DFA30990]; Gansu Provincial Science and Technology [Grant 0708WCGA14]; and the National Natural Science Foundation of China [Grant 2009AA01A130].

  • dx.doi.org/10.1124/mol.114.095208.

  • ↵Embedded ImageThis article has supplemental material available at molpharm.aspetjournals.org.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 87 (4)
Molecular Pharmacology
Vol. 87, Issue 4
1 Apr 2015
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Dehydrocrenatidine Is a Novel Janus Kinase Inhibitor
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Dehydrocrenatidine Is a Novel JAK Inhibitor

Jing Zhang, Ning Zhu, Yuping Du, Qifeng Bai, Xing Chen, Jing Nan, Xiaodong Qin, Xinxin Zhang, Jianwen Hou, Qin Wang and Jinbo Yang
Molecular Pharmacology April 1, 2015, 87 (4) 572-581; DOI: https://doi.org/10.1124/mol.114.095208

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Dehydrocrenatidine Is a Novel JAK Inhibitor

Jing Zhang, Ning Zhu, Yuping Du, Qifeng Bai, Xing Chen, Jing Nan, Xiaodong Qin, Xinxin Zhang, Jianwen Hou, Qin Wang and Jinbo Yang
Molecular Pharmacology April 1, 2015, 87 (4) 572-581; DOI: https://doi.org/10.1124/mol.114.095208
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
  • Relapsed-leukemia model with NT5C2/PRPS1 hotspot mutations
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics