Drug | Screening Assay CYP27A1 Activitya | Spectral Assay | logPc | |||||
---|---|---|---|---|---|---|---|---|
Apparent Kda | ∆Amaxb × 10−3 | λmin/λmax in Difference Spectrum | ||||||
% | µM | nm | ||||||
No drug | 100 | |||||||
Bicalutamide | 8 ± 1 | 3.4 ± 0.9 | 43 ± 4 | 385/418 | 2.5e | |||
Anastrozole | 13 ± 2 | 9.1 ± 2.1 | 16 ± 1 | 404/425 | 2.4e | |||
Dexmedetomidine | 17 ± 3 | 5.8 ± 0.1 | (1.5 ± 0.1) | 90 ± 1 | (42 ± 7) | 410/432 | (408/432) | 2.8e |
Fadrozole | 25 ± 3 | 20.4 ± 2.5 | (3.6 ± 0.1) | 55 ± 3 | (28 ± 2) | 410/429 | (408/428) | 2.3f |
Procarbazine | 52 ± 4 | NSRd | 0.1e | |||||
Thioperamide | 53 ± 3 | 18.1 ± 3.8 | 46 ± 3 | 409/432 | 3.2f | |||
Ravuconazole | 56 ± 3 | 3.9 ± 0.4 | (1.5 ± 0.2) | 32 ± 1 | (28 ± 2) | 389/423 | (382/416) | 3.9f |
Posaconazole | 57 ± 9 | 2.8 ± 0.1 | 13 ± 1 | 393/420 | 5.5e | |||
Letrozole | 62 ± 5 | NSR | 2.5e | |||||
Fluvoxamine | 62 ± 4 | NSR | 3.2e | |||||
Dacarbazine | 66 ± 3 | NSR | −0.2e | |||||
Aminolevulinic acid | 69 ± 5 | NSR | −1.5e | |||||
Crizotinib | 82 ± 12 | NSR | 1.8e | |||||
Aprepitant | 84 ± 8 | NSR | 4.5e | |||||
Exemestane | 87 ± 4 | NSR | 3.7e | |||||
Cisplatin | 89 ± 8 | NSR | −2.2e | |||||
Imexon | 90 ± 2 | NSR | −1.0f | |||||
Tranylcypromine | 94 ± 4 | NSR | 1.6e | |||||
Temozolomide | 95 ± 3 | NSR | −2.8e | |||||
Azacitidine | 95 ± 1 | NSR | −3.5e | |||||
Bexarotene | 96 ± 10 | NSR | 6.9e | |||||
Pamidronate | 97 ± 3 | NSR | −4.7e | |||||
Aminoglutethimide | 98 ± 2 | NSR | 1.3e | |||||
Clofarabine | 101 ± 3 | NSR | 0.0e | |||||
Vorinostat | 103 ± 4 | NSR | 2.0e | |||||
Axitinib | 104 ± 4 | NSR | 4.5e |
↵a Cholesterol 27-hydroxylation; all results represent mean ± S.D. of three independent measurements. Numbers in parentheses indicate binding parameters in the buffer lacking glycerol and NaCl.
↵b Normalized to micromoles of CYP27A1.
↵c logP, Octanol-water partition coefficient.
↵d NSR, no spectral response; the response was <0.009 absorbance units when 0.4 µM CYP27A1 was titrated up to an 18 µM drug.
↵e Experimental values.
↵f Theoretical values.