Repositioning Candidate Details
| Candidate ID: | R1190 |
| Source ID: | DB08949 |
| Source Type: | approved; withdrawn |
| Compound Type: | small molecule |
| Compound Name: | Inositol nicotinate |
| Synonyms: | hexanicotol; Inositol hexanicotinate; Inositol niacinate; Inositol nicotinate; mesoinositol hexanicotinate; myo-inositol hexanicotinate |
| Molecular Formula: | C42H30N6O12 |
| SMILES: | O=C(O[C@H]1[C@H](OC(=O)C2=CC=CN=C2)[C@@H](OC(=O)C2=CC=CN=C2)[C@H](OC(=O)C2=CC=CN=C2)[C@H](OC(=O)C2=CC=CN=C2)[C@@H]1OC(=O)C1=CC=CN=C1)C1=CC=CN=C1 |
| Structure: |
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| DrugBank Description: | Inositol nicotinate, also known as Inositol hexaniacinate/hexanicotinate or "no-flush niacin", is a niacin ester and vasodilator. It is used in food supplements as a source of niacin (vitamin B3), where hydrolysis of 1 g (1.23 mmol) inositol hexanicotinate yields 0.91 g nicotinic acid and 0.22 g inositol. Niacin exists in different forms including nicotinic acid, nicotinamide and other derivatives such as inositol nicotinate. It is associated with reduced flushing compared to other vasodilators by being broken down into the metabolites and inositol at a slower rate. Nicotinic acid plays an essential role in many important metabolic processes and has been used as lipid-lowering agent. Inositol nicotinate is prescribed in Europe under the name Hexopal as a symptomatic treatment for severe intermittent claudication and Raynaud’s phenomenon. |
| CAS Number: | 6556-11-2 |
| Molecular Weight: | 810.732 |
| DrugBank Indication: | Indicated as a dietary supplement for the source of niacin. Has been investigated for potential beneficial effects on serum lipids. In Europe, inositol hexanicotinate is indicated as a patented drug known as Hexopal, which is therapeutically indicated for the symptomatic relief of severe intermittent claudication and Raynaud’s phenomenon. |
| DrugBank Pharmacology: | Inositol nicotinate mediates a vasodilatory, lipid-lowering and fibrinolytic effect on the cardiovascular system. Like other niacins, inositol nicotinate is a lipid-regulating agent that reduces the levels of plasma triglycerides, atherogenic apolipoprotein B (apoB)-containing lipoproteins (VLDL, LDL and lipoprotein a) while increasing antiatherogenic apoA-I-containing HDL levels . |
| DrugBank MoA: | Inositol nicotinate and other niacins directly and noncompetitively inhibit microsomal enzyme diacylglycerol acyltransferase 2 (DGAT2) responsible for esterification of fatty acids to form triglycerides, resulting in decreased triglyceride synthesis and hepatic atherogenic lipoprotein secretion. Inhibitied triglyceride synthesis results in accelerated intracellular hepatic apo B degradation and the decreased secretion of VLDL and LDL particles . Niacin also inhibits hepatic expression of beta-chain adenosine triphosphate synthase which inhibits the removal or uptake of HDL–apo A-I. It is also suggested that niacin increases vascular endothelial cell redox state, resulting in the inhibition of oxidative stress and vascular inflammatory genes or key cytokines involved in atherosclerosis. It acts as a ligand on G-protein coupled receptor 109A (HCAR2/HM74A) and 109B (HCAR3/HM74) which mediates the anti-lipolytic and lipid-lowering effects of nicotinic acid. Niacin-mediated signalling of GPR109A expressed on adipocytes and G(i)-mediated decrease in cAMP levels result in decreased lipolysis, fatty acid mobilization, and triglyceride synthesis. The action of inositol nicotinate on GPR109A expressed on skin and macrophages to cause increased prostaglandin D2/E2 activity is thought to be less significant compared to other niacin molecules as it involves sustained release that leads to less flushing . |
| Targets: | Hydroxycarboxylic acid receptor 3 agonist; Hydroxycarboxylic acid receptor 2 agonist |
| Inclusion Criteria: | Therapeutic strategy associated |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs | |
|---|---|---|---|---|---|
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I07 | 1936 | Arteriosclerosis | Build-up of fatty material and calcium deposition in the arterial wall resulting in partial or complete occlusion of the arterial lumen.https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&ns=ncit&code=C35768 | disease of anatomical entity/cardiovascular system disease/ vascular disease/ artery disease | Details |