Table 3 ACC 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NCT02100527 (withdrawn)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)

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

K_i: 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