TABLE 1 .
Some of the properties of the strong CYP27A1 inhibitors
The alphabetical list of submicromolar CYP27A1 inhibitors is followed by the alphabetical list of low micromolar CYP27A1 inhibitors. The black line separates the two groups of inhibitors. Assay conditions are described under Material and Methods. Ki values represent the geometric mean of measurements from three independent experiments; the geometric S.D. factor is shown in parenthesis. Residual CYP27A1 activity in the screening assay represents the means ± S.D. of measurements from three independent experiments.
| Drug | Indication (Drug Target) | Ki | CYP27A1 Spectral Response | Cholesterol 27-Hydroxylation |
|---|---|---|---|---|
| μM | λmax /λmin in Difference Spectrum | %a | ||
| No drug | 100 ± 3 | |||
| Clevidipine | Hypertension (calcium channel) | 0.10 (1.04) | 433/412 | NDb |
| Delavirdine | HIV (reverse transcriptase) | 0.46 (1.09) | 426/403 | 2 ± 1 |
| Etravirine | HIV (reverse transcriptase) | 0.10 (1.14) | 385/418 | 2 ± 1 |
| Felodipine | Hypertension (calcium channel) | 0.47 (1.07) | 433/412 | ND |
| Nicardipine | Hypertension (calcium channel) | 0.76 (1.20) | 433/412 | ND |
| Nilotinib | Leukemia (tyrosine kinase) | 0.19 (1.09) | 435/412 | 2 ± 1 |
| Sorafenib |
Thyroid cancer (tyrosine kinase) |
0.18 (1.02) |
393/427 |
2 ± 1 |
| Abiratone | Prostate cancer (CYP17A1) | 1.57 (1.06) | 417/407 | 5 ± 1 |
| Candesartan | Hypertension (angiotensin II receptor) | 3.71 (1.13) | 436/414 | 11 ± 5 |
| Celecoxib | NSAID (cyclo-oxygenase 2)c | 7.72 (1.04) | 385/419 | 14 ± 5 |
| Dasatinib | Leukemia (tyrosine kinase) | 10.1 (1.06) | ND | 27 ± 2 |
| Nilvadipine | Hypertension (calcium channel) | 3.35 (1.03) | 433/412 | 7 ± 3 |
| Nimodipine | Hypertension (calcium channel) | 4.64 (1.07) | 433/413 | 10 ± 2 |
| Regorafenib | Colorectal cancer (tyrosine kinase) | 1.77 (1.07) | 406/426 | NDb |
Activity in the screening enzyme assay.
ND, not detectable; the limit of detection was 1% of cholesterol 27-hydroxylation in the screening enzyme assay and 0.002 absorbance units in the spectral assay.
NSAID, nonsteroidal anti-inflammatory drug.