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The role of carbonyl reductase 1 in drug discovery and development

Sophia M Shi1, Li Di2

  • 1a Cornell University , Ithaca , NY , USA.

Expert Opinion on Drug Metabolism & Toxicology
|July 18, 2017
PubMed
Abstract

Insights

Carbonyl reductase 1 (CBR1) is crucial for metabolizing drugs like ketones and aldehydes. Further research is needed to fully understand CBR1

Area of Science:

  • Pharmacology
  • Enzymology
  • Drug Metabolism

Background:

  • Carbonyl reductase 1 (CBR1) is a key enzyme in the metabolism of ketones and aldehydes.
  • CBR1 exhibits broad substrate specificity, influencing the disposition of numerous clinically significant drugs.
  • Understanding CBR1's role is vital due to its involvement in drug metabolism and potential for drug-drug interactions.

Purpose of the Study:

  • To comprehensively review the impact of Carbonyl reductase 1 (CBR1) on drug metabolism and disposition.
  • To detail the characteristics of the CBR1 enzyme, including its distribution, variability, and interactions.
  • To compare the structure and function of CBR1 with CBR3 and review chiral alcohol formation.

Main Methods:

  • Literature review and synthesis of existing research on CBR1.
  • Comparative analysis of CBR1 and CBR3 structure and function.
  • Review of studies on CBR1 substrate specificity, genetic polymorphism, and drug interactions.

Main Results:

  • CBR1 significantly impacts drug metabolism, affecting drug clearance and efficacy.
  • Factors like genetic variability, disease state, and enzyme induction influence CBR1 activity.
  • CBR1 plays a role in the formation of chiral alcohols and is implicated in drug-drug interactions.

Conclusions:

  • CBR1 is an emerging target in drug discovery, requiring further investigation.
  • In vitro-in vivo correlations for CBR1-mediated clearance and selective inhibitors require more characterization.
  • Understanding CBR1 regulation and its impact on individual variability and drug interactions is crucial for future drug development.
Keywords:
Carbonyl reductase 1genetic polymorphisminductionmetabolismspecies differencetissue distribution

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