Table 2.
ACLY inhibitors
| Compound (developer) | Potency in biochemical assays | Indication and/or preclinical effects | Clinical trial ID or refs |
|---|---|---|---|
| Clinical stage inhibitors | |||
| Bempedoic acid (Esperion Therapeutics, USA) | Ki: 2 μM | Primary hypercholesterolaemia and established atherosclerotic cardiovascular disease | Approved |
| Hydroxycitrate | Ki: 0.15 μM | Obesity and type 2 diabetes | NCT01238887 and NCT00699413 (terminated, phases I and IV) |
| Urine chemistries | NCT03348228 (in progress) | ||
| Preclinical stage inhibitors | |||
| BMS-303141 (Bristol-Myers Squibb Pharmaceutical Research Institute, USA) | IC50: 0.13 μM | Reduced weight gain, plasma lipids and glycaemia, and inhibited cancer cell growth | 94,160 |
| Emodin derivates (Harvard Medical School, USA) | IC50: 3–30 μM | Inhibited cancer cell growth | 155 |
| Furan carboxylate derivates (Harvard Medical School, USA) | IC50: 4.1–11.9 μM | Inhibited cancer cell growth | 159 |
| MEDICA 16 (Hadassah Medical School, Israel) | Ki: 16 μM | Reduced weight gain, hepatic steatosis, plasma lipids and atherosclerosis | 162,177,178 |
| SB-204990 (SmithKline Beecham Pharmaceuticals, UK) | Ki: 1 μM | Lowered plasma lipids and inhibited tumour growth | 86,158 |
| Discovery stage inhibitor | |||
| NDI-091143 (Nimbus Therapeutics, USA) | Ki: 0.07 μM | No functional studies reported | 161 |
ACLY, ATP-citrate lyase; IC50, half-maximal inhibitory concentration; Ki, inhibition constant.