TABLE 1

Profiling of BMS-423526 and four reference statins in enzymatic and cell-based selectivity assays

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Assay Data
BMS-423526
Cerivastatin
Atorvastatin
Rosuvastatin
Pravastatin
Rat HMGRa 1.3 ± 0.4 9.8 ± 2.8 6.2 ± 1.7 3.1 ± 0.4 31.6 ± 4.4
IC50 ± S.D. (nM)
Rat 1° hepa 4.5 ± 0.3 2.3 ± 0.6 2.5 ± 1.1 0.6 ± 0.2 28.4 ± 4.9
IC50 ± S.D. (nM)
Rat L6 myoa 2.3 ± 0.2 1.7 ± 0.9 77.1 ± 31.0 64.5 ± 30.1 1520 ± 514
IC50 ± S.D. (nM)
IC50 ratio 0.5 0.7 31.4 113.8 53.5
(L6/Hep)
Lipophilicityb 4.8 4.5 3.8 2.4 2.2
(log D7.0)

  • hep, hepatocyte.

  • ↵ a Mean IC50 values ± standard deviation (n ≥ 2 for each statin tested).

  • ↵ b Distribution coefficient measurements (log D7.0) for hydroxyacid forms of reference statins.