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Dietary Carbohydrate Restriction in the Management of NAFLD and Metabolic Syndrome
Published in Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss, Nutrition and Cardiometabolic Health, 2017
Grace Marie Jones, Kathleen Mulligan, Jean-Marc Schwarz, Nathalie Bergeron, Patty W. Siri-Tarino, George A. Bray, Ronald M. Krauss
A second synthetic molecule, aramchol, composed of cholic acid, a bile acid, and arachidic acid, a saturated FA, functions to inhibit stearoyl coenzyme A desaturase 1 (SCD1). SCD1 is an enzyme involved in the biosynthesis of FAs, and preclinical studies have shown that its inhibition decreases the synthesis of FAs and increases β-oxidation in the liver and brown adipose tissue (Dobrzyn, Dobrzyn et al. 2004, Dobrzyn and Ntambi 2005). Recently, a randomized 3-month trial demonstrated the efficacy and short-term safety of aramchol in people with NAFLD (n = 20) (Safadi, Konikoff et al. 2014). Specifically, there was an average 12.6% decrease in liver fat in those randomized to aramchol compared to a 6.4% increase in liver fat in the control group. While these results are promising, the long-term effects of aramchol have not yet been evaluated.
Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage
Published in Drug Development and Industrial Pharmacy, 2019
Xue-Yuan Jin, Chuan-Bao Zhu, Shi-Yong Fan, Jia-Lin Sun, Yu-Cong Shi, Chu-Han Wang, Hui-Fen Wang, Bo-Hua Zhong, Yi-Shan Yao, Wei-Guo Shi
Aramchol was initially synthesized as a cholesterol solubilizer to prevent the formation of cholesterol gallstones and has been newly applied for the treatment of nonalcoholic steatohepatitis in a clinical trial [15–19]. It is made by conjugating arachidic acid and 3-NH2 cholic acid (CA) via an amide bond. The 3-NH2 CA is derived from CA by conversion of the original 3-OH of bile acid to 3-NH2. However, this transformation changes the specific molecular structure of bile acid irreversibly, which may result in unpredictable toxicity or side effects. The UDCA-LPE conjugate is formed by coupling of the 24-COOH of ursodeoxycholic acid (UDCA) with lysophosphatidylethanolamine, which is a phosphatidylcholine precursor. However, the intact 24-COOH function group of bile acid is essential for liver specificity. Conjugation to the 24-COOH group may thus abolish the targeting of UDCA. Moreover, UDCA-LPE must be administrated by injection, which limits its clinical use.
Anti-diabetic drugs and NASH: from current options to promising perspectives
Published in Expert Opinion on Investigational Drugs, 2021
Sarra Smati, Clémence M Canivet, Jérôme Boursier, Bertrand Cariou
Arachidyl-amido cholanoic acid (Aramchol) is a novel fatty acid bile acid conjugate targeting stearoyl-coenzyme A desaturase-1, a key enzyme in hepatic lipogenesis. In a phase 2b randomized placebo-controlled trial, Aramchol 600 mg arm had significantly higher rates of NASH resolution without worsening of fibrosis and better glycemic control as evaluated by HbA1C (p < 0.001 versus placebo) [109]. A phase III clinical trial evaluating Aramchol in NASH is ongoing (ARMOR; NCT04104321).
An update on drug development for the treatment of nonalcoholic fatty liver disease – from ongoing clinical trials to future therapy
Published in Expert Review of Clinical Pharmacology, 2021
Aramchol is a liver-targeted steroyl-CoA desaturase (SCD-1) inhibitor. SCD-1 represents a key enzyme in hepatic lipogenesis that converts saturated fatty acids into monounsaturated fatty acids. In a one year phase 2 study, Aramchol showed liver fat reduction, biochemical improvement, NASH resolution, and fibrosis reduction in a dose-dependent manner [47]. Aramchol is currently being tested in a phase 3/4 ARMOR clinical trial (NCT04104321).