Investigational Drug Details
| Drug ID: | D367 |
| Drug Name: | Thioctic acid |
| Synonyms: | (+)-alpha-Lipoic acid; (R)-(+)-Lipoate; (R)-(+)-lipoic acid; (R)-1,2-Dithiolane-3-pentanoic acid; (R)-1,2-dithiolane-3-valeric acid; (R)-6,8-thioctic acid; (R)-lipoic acid; Alpha lipoic acid; alpha-Lipoic acid; D-thioctic acid; Lipoic acid; R-(+)-thioctic acid; R-alpha-lipoic acid; Thioctic acid; Thioctic acid D-form; α-lipoic acid |
| Type: | Chemical drug |
| DrugBank ID: | DB00166 |
| DrugBank Description: | A vitamin-like antioxidant. |
| PubChem ID: | 864 |
| CasNo: | 1077-28-7 |
| Repositioning for NAFLD: | Yes |
| SMILES: | C(CCCC(=O)O)C1CCSS1 |
| Structure: |
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| InChiKey: | AGBQKNBQESQNJD-UHFFFAOYSA-N |
| Molecular Weight: | 206.332 |
| DrugBank Targets: | Lipoyltransferase 1, mitochondrial; Lipoyl synthase, mitochondrial; Sodium-dependent multivitamin transporter |
| DrugBank MoA: | Lipoic Acid is generally involved in oxidative decarboxylations of keto acids and is presented as a growth factor for some organisms. Lipoic acid exists as two enantiomers, the R-enantiomer and the S-enantiomer. Normally only the R-enantiomer of an amino acid is biologically active, but for lipoic acid the S-enantiomer assists in the reduction of the R-enantiomer when a racemic mixture is given. Some recent studies have suggested that the S-enantiomer in fact has an inhibiting effect on the R-enantiomer, reducing its biological activity substantially and actually adding to oxidative stress rather than reducing it. Furthermore, the S-enantiomer has been found to reduce the expression of GLUT-4s in cells, responsible for glucose uptake, and hence reduce insulin sensitivity. |
| DrugBank Pharmacology: | Lipoic acid (or α-lipoic acid) is able to pass the blood-brain barrier and is putatively used for detoxification of mercury attached to the brain cells. It can mobilise bound mercury into the blood stream as it is a mercaptan (sulfur compound which readily binds to the mercury). In the blood stream, another chelator such as dimercaptosuccinic acid (DMSA) or methylsulfonylmethane (MSM) is used to transfer mercury safely into the urine for excretion. Neither DMSA nor MSM can cross the blood-brain barrier, which is why both lipoic acid and DMSA are used. It is hypothesized that this treatment-along with carnitine, dimethylglycine (DMG), Vitamin B6, folic acid, and magnesium—could be used to treat autism and amalgam poisoning. In this hypothesis, the reason why autism is difficult to treat is that mercury is attached to the brain cells and most medicines and vitamin supplements do not penetrate the blood-brain barrier. However, α-lipoic acid and perhaps vitamin B12 could making it possible for other chelators to remove mercury safely out of the body and could perhaps one day be used as a treatment for autism. Because lipoic acid is related to cellular uptake of glucose and it is both soluble in water and fat, it is being used for treatment in diabetes. It may be helpful for people with Alzheimer's disease or Parkinson's disease. |
| DrugBank Indication: | For nutritional supplementation, also for treating dietary shortage or imbalance. |
| Targets: | -- |
| Therapeutic Category: | Vitamin source drug |
| Clinical Trial Progress: | Phase 4 terminated (NCT01406704: Because of withdrawal of Avandia sale due to its risks outweigh its benefits) |
| Latest Progress: | Under clinical trials |
| Trial ID | Source ID | Phases | Status | Study Results | Start Date | Last Update Posted |
|---|
| Article ID | PMID | Source | Title | |
|---|---|---|---|---|
| A02739 | 34264552 | Vopr Pitan | [Pathogenetic mechanisms for the development of hematological disorders in induced fatty liver disease in Wistar rats and assessment of the regulatory effects of carnosine and α-lipoic acid]. | Details |
| A02910 | 34200615 | Nutrients | Lipoic Acid Exacerbates Oxidative Stress and Lipid Accumulation in the Liver of Wistar Rats Fed a Hypercaloric Choline-Deficient Diet. | Details |
| A04061 | 33772908 | Biofactors | The role of biofactors in the prevention and treatment of age-related diseases. | Details |
| A05549 | 33211913 | Vopr Pitan | [Effect of carnosine and α-lipoic acid on hepatocyte apoptosis and the cytokine profile in induced fatty liver disease in Wistar rats]. | Details |
| A10421 | 31343010 | Food Funct | Oral α-lipoic acid supplementation in patients with non-alcoholic fatty liver disease: effects on adipokines and liver histology features. | Details |
| A12140 | 30585337 | J Clin Pharm Ther | The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. | Details |
| A15109 | 29090431 | J Endocrinol Invest | Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients. | Details |
| A20637 | 25841776 | Free Radic Biol Med | Essential role of Nrf2 in the protective effect of lipoic acid against lipoapoptosis in hepatocytes. | Details |
| A21653 | 25152027 | Acta Pharmacol Sin | Alpha-lipoic acid attenuates insulin resistance and improves glucose metabolism in high fat diet-fed mice. | Details |
| A22715 | 24361606 | Biochim Biophys Acta | Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: role of oxidative stress. | Details |
| A22761 | 24325457 | J Med Food | The effects of α-lipoic acid on liver oxidative stress and free fatty acid composition in methionine-choline deficient diet-induced NAFLD. | Details |
| A22957 | 24176233 | Nutr Res | Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease. | Details |
| A23603 | 23634883 | Lipids Health Dis | Flaxseed oil and alpha-lipoic acid combination ameliorates hepatic oxidative stress and lipid accumulation in comparison to lard. | Details |
| A24472 | 22863080 | Liver Int | α-lipoic acid prevents non-alcoholic fatty liver disease in OLETF rats. | Details |
| A24520 | 22819708 | Eur J Pharmacol | Alpha-lipoic acid induces adipose triglyceride lipase expression and decreases intracellular lipid accumulation in HepG2 cells. | Details |
| A24948 | 22327056 | Obesity (Silver Spring) | Lipoic acid improves mitochondrial function in nonalcoholic steatosis through the stimulation of sirtuin 1 and sirtuin 3. | Details |
| A25122 | 22154902 | Life Sci | Alpha-lipoic acid attenuates methionine choline deficient diet-induced steatohepatitis in C57BL/6 mice. | Details |
| A25209 | 22093454 | Liver Int | Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction. | Details |
| A45338 | 25123628 | J Nutr Biochem | Alpha-lipoic acid improves high-fat diet-induced hepatic steatosis by modulating the transcription factors SREBP-1, FoxO1 and Nrf2 via the SIRT1/LKB1/AMPK pathway. | Details |
| A45531 | 24104204 | Physiol Genomics | Characterization of genome-wide transcriptional changes in liver and adipose tissues of ZDF (fa/fa) rats fed R-α-lipoic acid by next-generation sequencing. | Details |