Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
Pharmacological Reviews
  • 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
Pharmacological Reviews

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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 Pharm Rev on Facebook
  • Follow Pharm Rev on Twitter
  • Follow ASPET on LinkedIn
Review ArticleReview Article

Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application

Vindhya Koppaka, David C. Thompson, Ying Chen, Manuel Ellermann, Kyriacos C. Nicolaou, Risto O. Juvonen, Dennis Petersen, Richard A. Deitrich, Thomas D. Hurley and Vasilis Vasiliou
David R. Sibley, ASSOCIATE EDITOR
Pharmacological Reviews July 2012, 64 (3) 520-539; DOI: https://doi.org/10.1124/pr.111.005538
Vindhya Koppaka
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David C. Thompson
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ying Chen
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Manuel Ellermann
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kyriacos C. Nicolaou
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Risto O. Juvonen
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dennis Petersen
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard A. Deitrich
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thomas D. Hurley
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vasilis Vasiliou
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David R. Sibley
Departments of Pharmaceutical Sciences (V.K., Y.C., D.P., V.V.) and Clinical Pharmacy (D.C.T.), School of Pharmacy, and Department of Pharmacology, School of Medicine (R.A.D.), University of Colorado Anschutz Medical Campus, Aurora, Colorado; Department of Chemistry (M.E., K.C.N.) and Skaggs Institute of Chemical Biology (K.C.N.), the Scripps Research Institute, La Jolla, California; Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California (K.C.N.); School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland (R.O.J.); and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana (T.D.H.)
Roles: ASSOCIATE EDITOR
  • 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
Loading

Abstract

Aldehyde dehydrogenases (ALDHs) belong to a superfamily of enzymes that play a key role in the metabolism of aldehydes of both endogenous and exogenous derivation. The human ALDH superfamily comprises 19 isozymes that possess important physiological and toxicological functions. The ALDH1A subfamily plays a pivotal role in embryogenesis and development by mediating retinoic acid signaling. ALDH2, as a key enzyme that oxidizes acetaldehyde, is crucial for alcohol metabolism. ALDH1A1 and ALDH3A1 are lens and corneal crystallins, which are essential elements of the cellular defense mechanism against ultraviolet radiation-induced damage in ocular tissues. Many ALDH isozymes are important in oxidizing reactive aldehydes derived from lipid peroxidation and thereby help maintain cellular homeostasis. Increased expression and activity of ALDH isozymes have been reported in various human cancers and are associated with cancer relapse. As a direct consequence of their significant physiological and toxicological roles, inhibitors of the ALDH enzymes have been developed to treat human diseases. This review summarizes known ALDH inhibitors, their mechanisms of action, isozyme selectivity, potency, and clinical uses. The purpose of this review is to 1) establish the current status of pharmacological inhibition of the ALDHs, 2) provide a rationale for the continued development of ALDH isozyme-selective inhibitors, and 3) identify the challenges and potential therapeutic rewards associated with the creation of such agents.

Footnotes

  • This article is available online at http://pharmrev.aspetjournals.org.

    http://dx.doi.org/10.1124/pr.111.005538.

  • 1 Abbreviations:

    ALDH
    aldehyde dehydrogenase
    AMPAL
    4-amino-4-methyl-2-pentyne-1-al
    BIC
    butyl isocyanate
    CSC
    cancer stem cell
    CysBT
    S-(N-butylcarbamoyl)cysteine
    DDTC
    diethyldithiocarbamate
    DEAB
    4-(diethylamino)benzaldehyde
    DETC
    S-methyl-N,N-diethyldithiocarbamate
    DETC-SO
    S-methyl-N,N-diethyldithiocarbamate sulfoxide
    DTT
    dithiothreitol
    GSBT
    S-(N-butylcarbamoyl)GSH
    GTN
    glyceryl trinitrate
    ISDN
    isosorbide dinitrate
    MBT
    S-methyl-N-butylthiocarbamate
    Me-DDTC
    S-methyl-N,N-diethyldithiocarbamate
    Me-DDTC-SO
    S-methyl-N,N-diethylthiocarbamate-sulfoxide
    Me-DDTC-SO2
    S-methyl-N,N-diethylthiocarbamate-sulfone
    NAcSBT
    N-acetyl-S-(N-butylcarbamoyl)cysteine
    P450
    cytochrome P450
    RA
    retinoic acid.

  • © 2012 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

PharmRev 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

Pharmacological Reviews: 64 (3)
Pharmacological Reviews
Vol. 64, Issue 3
1 Jul 2012
  • 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 Pharmacological Reviews 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.
Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application
(Your Name) has forwarded a page to you from Pharmacological Reviews
(Your Name) thought you would be interested in this article in Pharmacological Reviews.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Review ArticleReview Article

ALDEHYDE DEHYDROGENASE INHIBITORS

Vindhya Koppaka, David C. Thompson, Ying Chen, Manuel Ellermann, Kyriacos C. Nicolaou, Risto O. Juvonen, Dennis Petersen, Richard A. Deitrich, Thomas D. Hurley and Vasilis Vasiliou
Pharmacological Reviews July 1, 2012, 64 (3) 520-539; DOI: https://doi.org/10.1124/pr.111.005538

Citation Manager Formats

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

Share
Review ArticleReview Article

ALDEHYDE DEHYDROGENASE INHIBITORS

Vindhya Koppaka, David C. Thompson, Ying Chen, Manuel Ellermann, Kyriacos C. Nicolaou, Risto O. Juvonen, Dennis Petersen, Richard A. Deitrich, Thomas D. Hurley and Vasilis Vasiliou
Pharmacological Reviews July 1, 2012, 64 (3) 520-539; DOI: https://doi.org/10.1124/pr.111.005538
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • I. Introduction
    • II. The Aldehyde Dehydrogenase Superfamily of Enzymes
    • III. Clinical Applications of Aldehyde Dehydrogenase Inhibitors
    • IV. Pharmacological Inhibitors of Aldehyde Dehydrogenase Enzymes
    • V. Concluding Remarks
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Review of Natural Language Processing in Pharmacology
  • PHARMACOGENOMICS: Driving Personalized Medicine
  • Potassium Channels in Parkinson's Disease
Show more Review Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Pharmacological Reviews
  • 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
  • Molecular Pharmacology
  • Pharmacology Research & Perspectives
ISSN 1521-0081 (Online)

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