Product name
Inhibitors of Aldosterone Synthase from ElexoPharm, SaarbrueckenSummary
A novel therapeutic strategy for the treatment of congestive heart failure, mycardial fibrosis and hyperalderonismOrganization name
ElexoPharm GmbHProfile
Background
In industrialized nations, cardiovascular diseases like congestive heart failure, myocardial fibrosis and hyperaldosteronism remain the leading killers for both men and women among all racial and ethnic groups. In the USA alone, the 2005 costs are estimated to be $300 billion and the burden continues to grow as the population ages.
The current strategy for the treatment of these deseases is to use mineralocorticoid receptor antagonists, heart glycosides, diuretics, AT-II receptor antagonists and ACE inhibitors.
It has long been recognized that abnormalities in the activity of aldosterone synthase cause chronic elevations of plasma aldosterone resulting in increased blood volume, stimulation of cardiac fibroblasts, cardiac hypertrophy, myocardial fibrosis and ventricular arrhythmia. Aldosterone, the most potent of all mineralocorticoids, is synthesized by the aldosterone synthase CYP11B2, the key enzyme of the mineralocorticoid biosynthesis.
We identified CYP11B2 as a novel target for a new therapeutic approach of the above mentioned diseases. The targeted inhibition of CYP11B2 by the highly specific non-steroidal inhibitor structure SL-125 reduces pathological levels of disease-associated aldosterone, thereby reducing the general risk of certain cardiovascular diseases.
Summary of Invention (lead structure SL125)
We identified the lead structure SL125 as a potent and highly selective inhibitor of CYP11B2 with IC50 values within the low nanomolar range for the treatment of congestive heart failure, myocardial fibrosis and hyperaldosteronism.
SL125 does not interfere with other related CYP enzymes like CYP11B1, CYP11A1, aromatase (CYP19) or 17α-hydroxylase (CYP17) and hepatic CYP enzymes (CYP1A2, CYP3A4, CYP2D6, CYP2C9 and CYP2C19) that are essential for normal function. The compound can be administered orally and shows an excellent pharmacokinetic profile, half life of 3 hours and sufficient bioavailability. SL125 can be synthesized at high yield and low cost, the manufacturing process can easily be adapted to large scale production.
For additional information on the preclinical results, physical, chemical and pharmaceutical properties, and further lead molecules please check the attached pdf or contact the company directly via the feedback link provided below.
Description File
Investigators_brochure_CYP11B2.pdf
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