10,12-Tricosadiynoic acid

• CAT Number: I017310
• CAS Number: 66990-30-5
• Molecular Formula: C23H38O2
• Molecular Weight: 346.55
• Purity: ≥95%
• Synonyms: tricosa-10,12-diynoic acid
• InChI: InChI=1S/C23H38O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-23(24)25/h2-10,15-22H2,1H3,(H,24,25)
• InChIKey: DIEDVCMBPCRJFQ-UHFFFAOYSA-N
• SMILES: CCCCCCCCCCC#CC#CCCCCCCCCC(=O)O

10,12-Tricosadiynoic acid is a highly specific, selective, high affinity and orally active acyl-CoA oxidase-1 (ACOX1) inhibitor. 10,12-Tricosadiynoic acid can treat high fat diet- or obesity-induced metabolic diseases by improving mitochondrial lipid and ROS metabolism[1]. 10,12-Tricosadiynoic acid is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
10,12-Tricosadiynoic acid-CoA rapidly inhibits ACOX1 activity in a time- and concentration-dependent manner. The activity of ACOX1 decreases by nearly 95% after 5 min of incubation with 10 eq of 10,12-Tricosadiynoic acid-CoA. ACOX1 activity is inhibited only if free 10,12-Tricosadiynoic Acid is activated as the CoA thioester, the substrate form. Inhibition of ACOX1 by 10,12-Tricosadiynoic acid-CoA is irreversible. And the kinetics parameters KI and kinact are calculated to be 680 nm and 3.18 min 1, respectively[1].
10,12-Tricosadiynoic acid is the precursor of 10,12-Tricosadiynoic acid-CoA and is transformed into 10,12-Tricosadiynoic acid-CoA by peroxisomal very long chain acyl-CoA synthetase (VLACS) after entering into cells, and it inhibits ACOX1 in vivo[1].
10,12-Tricosadiynoic acid (500 nM) inhibits acyl-CoA oxidase-1 (ACOX1) activity. 10,12-Tricosadiynoic acid treatment abrogates the protective effect by Sirt5 siRNA[2].
10,12-Tricosadiynoic acid (100 μg/kg; oral gavage; daily; for 8 weeks; male Wistar rats) treatment increases hepatic mitochondrial fatty acid oxidation (FAO) via activation of the SIRT1-AMPK (adenosine 5′-monophosphate-activated protein kinase) pathway and proliferator activator receptor α and reduces hydrogen peroxide accumulation in high fat diet-fed rats, which significantly decreases hepatic lipid and ROS contents, reduces body weight gain, and decreases serum triglyceride and insulin levels[1].
10,12-Tricosadiynoic acid (0 mg/kg, 37.5 mg/kg, 75 mg/kg, and 150 mg/kg diet) treatment does not affect weight gain, but significantly decreases peroxisomal β-oxidation in the liver, and increased body fat accumulation in Nile tilapia. The fish with impaired peroxisomal β-oxidation exhibited higher contents of serum lipid and peroxidation products, and alanine aminotransferase activity, and significantly lowered hepatic activities of superoxide dismutase and catalase[3].

Reference

[1]. Zeng J, et al. Specific Inhibition of Acyl-CoA Oxidase-1 by an Acetylenic Acid Improves Hepatic Lipid and Reactive Oxygen Species (ROS) Metabolism in Rats Fed a High Fat Diet. J Biol Chem. 2017 Mar 3;292(9):3800-3809.
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[2]. Takuto Chiba, et al. Sirtuin 5 Regulates Proximal Tubule Fatty Acid Oxidation to Protect against AKI. J Am Soc Nephrol. 2019 Dec;30(12):2384-2398.
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[3]. Yan Liu, et al. Impaired peroxisomal fat oxidation induces hepatic lipid accumulation and oxidative damage in Nile tilapia. Fish Physiol Biochem. 2020 Aug;46(4):1229-1242.
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