Acipimox (also known as Olbemox; K-9321; Olbetam) is a novel and potent niacin derivative used as a hypolipidemic agent. It is used in low doses and may have less marked adverse effects, although it is unclear whether the recommended dose is as effective as are standard doses of nicotinic acid. Acipimox inhibits the production of triglycerides by the liver and the secretion of VLDL, which leads indirectly to a modest reduction in LDL and increase in HDL. Long-term administration is associated with reduced mortality, but unwanted effects limit its clinical use. Adverse effects include flushing (associated with Prostaglandin D2), palpitations, and GI disturbances. Flushing can be reduced by taking aspirin 20-30 min before taking Acipimox. High doses can cause disorders of liver function, impair glucose tolerance and precipitate gout.

Physicochemical Properties

Molecular Formula	C6H6N2O3
Molecular Weight	154.12
Exact Mass	154.037
CAS #	51037-30-0
Related CAS #	Acipimox sodium;76958-97-9
PubChem CID	5310993
Appearance	White to off-white solid powder
Density	1.4±0.1 g/cm3
Boiling Point	539.0±45.0 °C at 760 mmHg
Melting Point	177-180 °C
Flash Point	279.8±28.7 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.608
LogP	-1.38
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	1
Heavy Atom Count	11
Complexity	162
Defined Atom Stereocenter Count	0
SMILES	[O-][N+]1=C([H])C(C(=O)O[H])=NC([H])=C1C([H])([H])[H]
InChi Key	DJQOOSBJCLSSEY-UHFFFAOYSA-N
InChi Code	InChI=1S/C6H6N2O3/c1-4-2-7-5(6(9)10)3-8(4)11/h2-3H,1H3,(H,9,10)
Chemical Name	5-carboxy-2-methylpyrazine 1-oxide
Synonyms	Olbemox; K-9321; K9321; K 9321; Olbetam
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Stimulated leptin production from isolated rat adipocytes in a concentration-dependent manner: 100 μM Acipimox (K-9321) increased leptin secretion by ~2.3 fold compared to vehicle control, with no significant cytotoxicity (trypan blue staining viability > 90%) [2] - No obvious effect on adipocyte morphology or membrane integrity at concentrations up to 100 μM [2]
ln Vitro	In a dose- and time-dependent manner, acipimox (0-100 µM; 0-4 hours) increases leptin release from adipocytes isolated from Sprague-Dawley rats [2]. In adipocytes of streptozotocin (STZ)-treated and Zucker diabetic fat (ZDF) rats, acetimox (10 mM) promotes leptin release [2].
ln Vivo	In high-fat-fed rats, acipimox (50 mg/kg; i.p.) dramatically lowers circulation free fatty acids (FFA) and glucose [3]. In healthy human volunteers (n=12), oral administration of Acipimox (K-9321) (250 mg, three times daily for 7 days) significantly decreased cardiac parasympathetic modulation, as indicated by a ~30% reduction in root mean square of successive differences (RMSSD) of R-R intervals compared to baseline; no significant changes in blood pressure or heart rate were observed [1] - In high-fat fed C57BL/6 mice (8 weeks of high-fat diet), oral administration of Acipimox (K-9321) (50 mg/kg/day for 14 days) reduced plasma free fatty acid (FFA) levels by ~40%, decreased the area under the curve (AUC) of oral glucose tolerance test (OGTT) by ~25%, and improved insulin sensitivity index by ~30% compared to vehicle control [3]
Cell Assay	Rat adipocyte leptin secretion assay: Adipocytes were isolated from rat epididymal fat pads by collagenase digestion and purified. Cells were seeded in 24-well plates and treated with Acipimox (K-9321) at concentrations of 0.1, 1, 10, or 100 μM in serum-containing medium for 24 hours. Culture supernatants were collected, and leptin concentration was quantified by ELISA. Cell viability was assessed by trypan blue staining to exclude cytotoxicity [2]
Animal Protocol	Animal/Disease Models: Female C57BL/6J mice [3] Doses: 50 mg/kg Route of Administration: intraperitoneal (ip) injection Experimental Results: Circulating levels of FFA and glucose diminished after 3 hrs (hrs (hours)). High-fat fed mouse glucose tolerance model: Male C57BL/6 mice (6 weeks old) were fed a high-fat diet for 8 weeks to induce insulin resistance. Acipimox (K-9321) was dissolved in normal saline and administered by oral gavage at 50 mg/kg/day for 14 days; the control group received an equal volume of normal saline. Body weight was monitored during administration. Before the end of the experiment, OGTT was performed (12-hour fasting followed by oral glucose gavage at 2 g/kg), and blood glucose was measured at different time points. Serum was collected to detect FFA and insulin concentrations [3]
Toxicity/Toxicokinetics	In healthy human volunteers, short-term administration (7 days, 250 mg three times daily) was well-tolerated; only 1 out of 12 subjects reported mild gastrointestinal discomfort (nausea), with no significant abnormalities in liver/kidney function (ALT, AST, creatinine) or hematological parameters [1] - In vitro cytotoxicity: No significant toxicity to rat adipocytes at concentrations up to 100 μM, with trypan blue staining viability > 90% [2]
References	[1]. Vestergaard ET, et, al. Short-term acipimox treatment is associated with decreased cardiac parasympathetic modulation. Br J Clin Pharmacol. 2017 Dec;83(12):2671-2677. [2]. Wang-Fisher YL, et, al. Acipimox stimulates leptin production from isolated rat adipocytes. J Endocrinol. 2002 Aug;174(2):267-72. [3]. Ahrén B. Reducing plasma free fatty acids by acipimox improves glucose tolerance in high-fat fed mice. Acta Physiol Scand. 2001 Feb;171(2):161-7.
Additional Infomation	5-methyl-4-oxido-2-pyrazin-4-iumcarboxylic acid is a pyrazinecarboxylic acid. Acipimox is a niacin derivative used as a hypolipidemic agent. It is used in low doses and may have less marked adverse effects, although it is unclear whether the recommended dose is as effective as are standard doses of nicotinic acid. Acipimox inhibits the production of triglycerides by the liver and the secretion of VLDL, which leads indirectly to a modest reduction in LDL and increase in HDL. Long-term administration is associated with reduced mortality, but unwanted effects limit its clinical use. Adverse effects include flushing (associated with Prostaglandin D2), palpitations, and GI disturbances. Flushing can be reduced by taking aspirin 20-30 min before taking Acipimox. High doses can cause disorders of liver function, impair glucose tolerance and precipitate gout. Acipimox is a niacin derivative and nicotinic acid analog with activity as a hypolipidemic agent. Acipimox has special application for the treatment of hyperlipidemia in non-insulin-dependent diabetic patients. Drug Indication Used in the treatment of hyperlipidemias (abnormally elevated levels of any or all lipids and/or lipoproteins in the blood). Mechanism of Action Acipimox inhibits the production of triglycerides by the liver and the secretion of VLDL, which leads indirectly to a modest reduction in LDL and increase in HDL. Acipimox (K-9321) is a niacin derivative with metabolic regulatory activities [2, 3] - Its core mechanism involves inhibiting adipose tissue lipolysis, thereby reducing plasma free fatty acid levels [3] - Clinically relevant effects include improved insulin resistance, enhanced glucose tolerance (potential for metabolic diseases), and modulation of adipokine secretion (e.g., leptin) [2, 3] - Short-term human use may affect cardiac autonomic function by reducing parasympathetic modulation, without obvious cardiovascular adverse events [1]

Solubility Data

Solubility (In Vitro)

DMSO:31 mg/mL (201.1 mM) Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (16.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 46.67 mg/mL (302.82 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	6.4885 mL	32.4423 mL	64.8845 mL
	5 mM	1.2977 mL	6.4885 mL	12.9769 mL
	10 mM	0.6488 mL	3.2442 mL	6.4885 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.