Aldosterone synthase inhibition: cardiorenal protection in animal disease models and translation of hormonal effects to human subjects

Table 1 In vitro selectivity of LCI699 in human, rat and monkey enzymes

Assay	Aldosterone synthase (CYP11B2) IC₅₀, nmol/L	11β-hydroxylase (CYP11B1) IC₅₀, nmol/L	Selectivity ratio^a(CYP11B2:CYP11B1)
Recombinant human enzyme	0.7 ± 0.01 (6)	2.5 ± 0.1 (4)	3.6
Recombinant rat enzyme	160 ± 9 (3)	410 ± 5 (3)	2.6
Rat adrenal homogenate	802 (2)	3045 (2)	3.8
Monkey adrenal homogenate	12 ± 1 (6)	62 ± 5 (6)	5.2

Table shows selectivity ratios for LCI699 for inhibition of aldosterone synthase (CYP11B2) over 11β-hydroxylase (CYP11B1). All values are mean ± SEM (n) except for rat adrenal homogenate where only mean values from two experiments are presented.
^aSelectivity ratio is defined as the ratio of IC₅₀ values obtained in the CYP11B2 and CYP11B1 assays.
CYP, cytochrome P450; IC₅₀, half maximal inhibitory concentration.

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