Preliminary efficacy and safety of acetyl-CoA carboxylase inhibitor GS-0976 in patients with compensated cirrhosis due to NASH

Harrison, S.; Noureddin, Mazen; Herring, Robert; Ruane, P.; Mccolgan, B.; Kirby, Barbara D.; Nelson, Christian J.; Schall, Raul Aguilar; Jia, Chong-Qi; Subramanian, Madhu; Myers, R.; Middleton, Mark R.; Sirlin, Claude B.; Fitch, Mark; Li, K.; Hellerstein, Marc K.; Lawitz, Eric

doi:10.1016/s0168-8278(18)31425-9

Cited by 3 publications

(3 citation statements)

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Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

“…More recently, preliminary studies have evaluated the role of GS-0976 independently [ 68 , 69 , 70 ]. GS-0976 is an acetyl-coenzyme A carboxylase inhibitor, therefore inhibiting catalysis of de novo lipogenesis [ 68 ]. In a proof of concept, open-label study, treatment of 10 subjects with NASH with GS-0976 at 12 weeks resulted in decrease in hepatic de novo lipogenesis, proton density fat fraction, liver stiffness, and serum alanine transaminase, accompanied by favorable safety profile [ 68 , 69 , 70 ].…”

Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

“…GS-0976 is an acetyl-coenzyme A carboxylase inhibitor, therefore inhibiting catalysis of de novo lipogenesis [ 68 ]. In a proof of concept, open-label study, treatment of 10 subjects with NASH with GS-0976 at 12 weeks resulted in decrease in hepatic de novo lipogenesis, proton density fat fraction, liver stiffness, and serum alanine transaminase, accompanied by favorable safety profile [ 68 , 69 , 70 ]. A separate phase 2 randomized, double-blind, placebo controlled trial evaluating 127 patients with NASH is in progress (NCT 02856555) [ 71 ].…”

Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

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Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

Dibba

Perumpail

et al. 2018

Diseases

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The two main subsets of nonalcoholic fatty liver disease (NAFLD) include: (1) nonalcoholic fatty liver (NAFL), the more common and non-progressive subtype; and (2) nonalcoholic steatohepatitis (NASH), the less common subtype, which has the potential to progress to advanced liver damage. Current treatment strategies have focused on lifestyle management of modifiable risk factors, namely weight, and on the optimization of the management of individual components of metabolic syndrome. Various hypothetical pathogenic mechanisms have been proposed, leading to the development of novel drugs with the potential to effectively treat patients with NASH. Numerous clinical trials are ongoing, utilizing these experimental drugs and molecules targeting specific mechanistic pathway(s) to effectively treat NASH. Some of these mechanistic pathways targeted by experimental pharmacologic agents include chemokine receptor 2 and 5 antagonism, inhibition of galectin-3 protein, antagonism of toll-like receptor 4, variation of fibroblast growth factor 19, agonism of selective thyroid hormone receptor-beta, inhibition of apoptosis signal-regulating kinase 1, inhibition of acetyl-coenzyme A carboxylase, agonism of farnesoid X receptor, antibodies against lysl oxidase-like-2, and inhibition of inflammasomes. Emerging data are promising and further updates from ongoing clinical trials are eagerly awaited.

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Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

Section: Potential Drug Targets For the Treatment Of Nafldmentioning

confidence: 99%

See 1 more Smart Citation

Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

Dibba

Perumpail

et al. 2018

Diseases

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Progress in research of lipogenesis inhibitors for treatment of nonalcoholic fatty liver disease

Yang¹,

Li²,

Li³

2022

WCJD

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Recent Development in Acetyl-CoA Carboxylase Inhibitors and their Potential as Novel Drugs

Huang

2020

Future Med. Chem.

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Acetyl-CoA carboxylase (ACC), a critical enzyme in the regulation of fatty acid synthesis and metabolism, has emerged as an attractive target for a plethora of emerging diseases, such as diabetes mellitus, nonalcoholic fatty liver disease, cancer, bacterial infections and so on. With decades of efforts in medicinal chemistry, significant progress has been made toward the design and discovery of a considerable number of inhibitors of this enzyme. In this review, we not only clarify the role of ACC in emerging diseases, but also summarize recent developments of potent ACC inhibitors and discuss their molecular mechanisms of action and potentials as novel drugs as well as future perspectives toward the design and discovery of novel ACC inhibitors.

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Preliminary efficacy and safety of acetyl-CoA carboxylase inhibitor GS-0976 in patients with compensated cirrhosis due to NASH

Cited by 3 publications

References 0 publications

Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

Emerging Therapeutic Targets and Experimental Drugs for the Treatment of NAFLD

Progress in research of lipogenesis inhibitors for treatment of nonalcoholic fatty liver disease

Recent Development in Acetyl-CoA Carboxylase Inhibitors and their Potential as Novel Drugs

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