Table 2.
Comparison of anti-TG synthesis activities of twelve DGAT inhibitors based on their enzymatic specificity. IC50 (RM) values were previously determined by using a rat liver microsome [14,15]. IC50 (DGAT-1) values were previously determined by using a recombinant DGAT-1 and [14C] triglyceride from [14C] oleoyl-CoA as an acyl-donor [13,15]. IC50 (DGAT-2) values were previously determined by using a recombinant DGAT-2 [13,15]. TG% (10 µM in HepG2) were previously determined relative [14C] triglyceride percentages when treated with 10 μM in HepG2 cells by using [14C] glycerol as a substrate [13,15]. N/D means not determined.
| Species | Code | IC50 (RM) (μM) | IC50 (DGAT-1) (μM) | IC50 (DGAT-2) (μM) | TG % (10 μM in HepG2) |
|---|---|---|---|---|---|
| Benzimidazoles (pan DGATs inhibitors) | 10e | 27.5 | N/D | N/D | N/D |
| 10f | >50 | N/D | N/D | N/D | |
| 10h | >50 | N/D | N/D | N/D | |
| 10i | 20.0 | N/D | N/D | N/D | |
| 10j | 4.4 | 9.0 | 17.3 | 45.0 | |
| Indolyl hydrazides (DGAT-1 inhibitors) | 8h | N/D | 20.4 | >10 | 71.2 |
| 8i | N/D | 2.1 | >10 | 94.8 | |
| 8u | N/D | 1.5 | >10 | 55.7 | |
| Indolyl acrylamides (DGAT-2 inhibitors) | 5a | 8.8 | >100 | 6.9 | N/D |
| 5c | 13.2 | 89.1 | 6.8 | N/D | |
| 5h | 2.5 | >100 | 6.9 | 33.2 | |
| 5j | 9.4 | >100 | 7.4 | N/D | |
| DGAT-1 inhibitor | A922500 | N/D | 0.007 | N/D | N/D |