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The potential of targeting CYP11B
1a Lehrstuhl für Biochemie , Universität des Saarlandes , Saarbrücken , Germany.
Expert Opinion on Therapeutic Targets
|February 9, 2016
Summary
Developing drugs targeting CYP11B1 and CYP11B2 is promising for treating cortisol and aldosterone overproduction disorders. Selective inhibitors show potential, with early trials indicating therapeutic possibilities for conditions like hypertension.
Area of Science:
- Biochemistry
- Endocrinology
- Pharmacology
Background:
- The CYP11B subfamily, including CYP11B1 (cortisol synthesis) and CYP11B2 (aldosterone synthesis), is crucial for steroid hormone biosynthesis.
- Dysregulation of cortisol and aldosterone production is linked to Cushing's disease and hypertension, respectively, making these enzymes significant therapeutic targets.
Purpose of the Study:
- To review the functional and structural properties of CYP11B1 and CYP11B2.
- To discuss the development of screening systems for potential CYP11B1 and CYP11B2 inhibitors.
- To explore the development and testing of novel drugs targeting these enzymes.
Main Methods:
- Detailed description of CYP11B1 and CYP11B2 genes and proteins.
- Development and application of efficient test systems for inhibitor screening.
- Synthesis and evaluation of selective CYP11B1 and CYP11B2 inhibitors.
Main Results:
- Successful development of screening systems for CYP11B1 and CYP11B2 inhibitors.
- Demonstrated success in synthesizing selective inhibitors for these isoenzymes.
- Early clinical trials of CYP11B2 inhibitor LCI699 showed promise in animal models for end-organ damage inhibition.
Conclusions:
- Efficient screening systems and selective inhibitors provide a strong foundation for drug development targeting CYP11B1 and CYP11B2.
- LCI699, despite side effects, represents a potential lead compound for future therapeutic strategies against aldosterone-related conditions.
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