Table 3.
ACC inhibitors
| Compound (developer) | Potency in biochemical assays | Indication and/or preclinical effects | Clinical trial ID or refs |
|---|---|---|---|
| Clinical stage inhibitors | |||
| Firsocostat (Nimbus Therapeutics, USA) | IC50: 2.1 nM (hACC1), 6.1 nM (hACC2) | NASH | NCT02856555 (completed, phase II) |
| PF-05221304 (Pfizer Inc., USA) | IC50: 13 nM (hACC1), 9 nM (hACC2) | NAFLD–NASH | NCT03248882 (completed, phase II) |
| PF-05175157 (Pfizer Inc., USA) | IC50: 27 nM (hACC1), 33 nM (hACC2) | Type 2 diabetes | NCT01792635 (terminated, phase II) |
| Acne vulgaris | NCT02100527 (withdrawn) | ||
| MK-4074 (Merck &Co., USA) | IC50: ~3 nM (hACC1), ~3 nM (hACC2) | NAFLD | NCT01431521 (completed, phase I) |
| Preclinical stage inhibitors | |||
| A-908292 (Abbott Laboratories, USA) | IC50: >30 μM (hACC1), 0.023 μM (hACC2) | Reduced plasma lipids and glycaemia | 226 |
| Carboxamide derivative-1k (Takeda, Japan) | IC50: 170 nM (hACC1), 2 µM (hACC2) | Decreased malonyl-CoA in xenograft tumour | 209 |
| CP-640186 (Pfizer Inc., USA) | IC50: 53 nM (rACC1), 61 nM (rACC2) | Reduced weight gain, hepatic steatosis, plasma lipids and glycaemia, and inhibited cancer growth | 216,230 |
| Monocyclic derivate-1q (Takeda, Japan) | IC50: 0.58 nM(hACC1), >10 μM (hACC2) | Decreased malonyl-CoA in xenograft tumour | 208 |
| ND-654 (Nimbus Therapeutics, USA) | IC50: 3 nM (hACC1), 8 nM (hACC2) | Inhibited hepatocellular carcinoma growth, reduced hepatic steatosis and plasma lipids | 189 |
| ND-646 (Nimbus Therapeutics, USA) | IC50: 3.5 nM (hACC1), 4.1 nM (hACC2) | Inhibited tumour growth | 207 |
| Olefin derivate-2e (Shionogi & Co., Japan) | IC50: 1,950 nM (hACC1), 1.9 nM (hACC2) | Improved glucose homeostasis | 213 |
| (S)-9c (Boehringer Ingelheim Pharma GmbH & Co., USA) | IC50: >30 μM (hACC1), 0.07 μM (hACC2) | Improved glucose and lipid homeostasis | 212 |
| Soraphen A | Ki: 2.1 nM (yACC) | Reduced weight gain, improved insulin sensitivity and inhibited cancer cell growth | 214,228 |
| TOFA | IC50: 2.5 μM (rACC) | Reduced lipid synthesis, inflammation and cancer cell growth | 229 |
| WZ66 (China Pharmaceutical University, China) | IC50: 435.9 nM (hACC1), 141.3 nM (hACC2) | Reduced hepatic steatosis and hepatic stellate cell activation | 204 |
ACC, acetyl-CoA carboxylase; hACC, human ACC; IC50, half-maximal inhibitory concentration; Kd, dissociation constant; Ki, inhibition constant; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; rACC, rat ACC; yACC, yeast ACC.