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]

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].

In high-fat-fed rats, acipimox (50 mg/kg; i.p.) dramatically lowers circulation free fatty acids (FFA) and glucose [3].

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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]

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/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)).

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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]

In healthy volunteers, short-term administration (7 days, 250 mg three times daily) was well tolerated; only 1 of the 12 subjects reported mild gastrointestinal discomfort (nausea), and there were no significant abnormalities in liver and kidney function (ALT, AST, creatinine) or hematological parameters [1]
- In vitro cytotoxicity: At concentrations up to 100 μM, there was no significant toxicity to rat adipocytes, and trypan blue staining showed cell viability >90% [2]

[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.

5-Methyl-4-oxo-2-pyrazin-4-onthialic acid is a pyrazin carboxylic acid. Acipimox is a niacin derivative used as a lipid-lowering drug. It is usually used at low doses, and adverse reactions may be mild, but it is unclear whether the recommended dose is as effective as the standard dose of niacin. Acipimox inhibits the production of hepatic triglycerides and the secretion of very low-density lipoprotein (VLDL), thereby indirectly leading to a mild decrease in low-density lipoprotein (LDL) and an increase in high-density lipoprotein (HDL). Long-term use is associated with reduced mortality, but adverse reactions limit its clinical application. Adverse reactions include flushing (related to prostaglandin D2), palpitations, and gastrointestinal discomfort. Taking aspirin 20-30 minutes before taking acipimox can reduce flushing. High doses can cause liver dysfunction, impaired glucose tolerance, and induce gout. Acipimox is a niacin derivative and niacin analog with lipid-lowering activity. Acipimox is specifically indicated for the treatment of hyperlipidemia in patients with non-insulin-dependent diabetes mellitus. Drug Indications For the treatment of hyperlipidemia (abnormally elevated levels of any or all lipids and/or lipoproteins in the blood). Mechanism of Action Acipimox inhibits the production of triglycerides and the secretion of very low-density lipoprotein (VLDL) in the liver, thereby indirectly leading to a moderate decrease in low-density lipoprotein (LDL) and an increase in high-density lipoprotein (HDL).

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Acilimus (K-9321) is a nicotinic acid derivative with metabolic regulatory activity [2, 3]
- Its core mechanism is to inhibit lipolysis in adipose tissue, thereby reducing plasma free fatty acid levels [3]
- Clinically relevant effects include improving insulin resistance, enhancing glucose tolerance (reducing the risk of metabolic diseases), and regulating the secretion of adipokines (such as leptin) [2, 3]
- Short-term human use may affect cardiac autonomic function by reducing parasympathetic regulation, but does not induce significant adverse cardiovascular events [1]

C6H6N2O3

154.12

154.037

51037-30-0

Acipimox sodium;76958-97-9

5310993

White to off-white solid powder

1.4±0.1 g/cm3

539.0±45.0 °C at 760 mmHg

177-180 °C

279.8±28.7 °C

0.0±1.5 mmHg at 25°C

1.608

-1.38

1

4

1

11

162

0

[O-][N+]1=C([H])C(C(=O)O[H])=NC([H])=C1C([H])([H])[H]

DJQOOSBJCLSSEY-UHFFFAOYSA-N

InChI=1S/C6H6N2O3/c1-4-2-7-5(6(9)10)3-8(4)11/h2-3H,1H3,(H,9,10)

5-carboxy-2-methylpyrazine 1-oxide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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.

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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.

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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.

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)