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| 5mg |
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| 10mg |
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| 50mg | |||
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| Targets |
Nicodicosapent targets the sterol regulatory element-binding protein (SREBP), a key transcriptional regulator of cholesterol and fatty acid metabolism. SREBP controls the expression of multiple genes involved in lipid biosynthesis and uptake, including HMG-CoA reductase (the rate-limiting enzyme in cholesterol synthesis), PCSK9 (which regulates LDL receptor degradation), ATP citrate lyase (involved in fatty acid synthesis), and NPC1L1 (involved in cholesterol absorption). By inhibiting SREBP, Nicodicosapent reduces the expression of these target genes, leading to decreased cholesterol and triglyceride levels. The compound is a synthetic conjugate of EPA (an omega-3 fatty acid) and niacin, which may provide complementary lipid-lowering effects. The compound does not target a specific receptor but rather modulates lipid metabolism through SREBP inhibition.
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| ln Vitro |
Nicodicosapent does not interact with the GPR109A receptor, however it does decrease the mature SREBP-2 protein synthesis in HepG2 cells. With an IC50 value of 17 μM, nicodicosapent demonstrated synergistic inhibition of secreted PCSK9. With an IC50 of 27 μM, nicodicosapent substantially and dose-dependently suppresses ApoB secretion. In HepG2 cells, nicosapent induces hydrolysis in a time-dependent manner [1].
In vitro, Nicodicosapent inhibits SREBP activity, leading to reduced expression of SREBP target genes such as PCSK9, HMG-CoA reductase, ATP citrate lyase, and NPC1L1. In cell-based assays (e.g., HepG2 hepatoma cells), treatment with Nicodicosapent (1-100 μM) results in decreased cholesterol synthesis and reduced LDL receptor degradation (via PCSK9 downregulation). The compound also reduces triglyceride synthesis and secretion in hepatocytes. The niacin moiety may contribute additional lipid-modulating effects through the niacin receptor (GPR109A), although the primary mechanism is attributed to SREBP inhibition. Nicodicosapent's in vitro activity has been characterized in preclinical studies supporting its development as a lipid-lowering agent. The compound is soluble in DMSO (≥60 mg/mL), facilitating its use in in vitro assays. |
| ln Vivo |
Nicotinic acid is produced in large amounts in plasma by nicodicosapent (100 mg/kg po). Treatment with Nicodicosapent significantly decreased the levels of PCSK9, LDL particles (including VLDL and LDL cholesterol), and plasma triglycerides in ApoE*3-Leiden mice [1].
In vivo, Nicodicosapent has been evaluated in preclinical and clinical studies for the treatment of hypertriglyceridemia. In animal models, administration of Nicodicosapent reduces serum triglyceride and cholesterol levels. The compound is currently in Phase 2 clinical development, indicating that it has demonstrated promising efficacy and safety in early-stage clinical trials. The compound's mechanism of SREBP inhibition leads to downregulation of PCSK9, HMG-CoA reductase, and other lipid metabolism genes, resulting in improved lipid profiles. The EPA-niacin conjugate design may provide synergistic lipid-lowering effects compared to either component alone. Further clinical data will be needed to fully characterize its efficacy and safety in patient populations. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Nicodicosapent are not well-established as the compound's primary mechanism involves SREBP inhibition rather than direct enzyme inhibition or receptor binding. However, SREBP activity can be assessed using cell-based reporter assays. A typical protocol: HepG2 or HEK293 cells are transfected with an SREBP-responsive luciferase reporter plasmid (e.g., containing the LDL receptor promoter or other SREBP target gene promoter). Cells are treated with Nicodicosapent at concentrations ranging from 0.1 to 100 μM for 16-24 hours. Luciferase activity is measured using a luminometer, and IC₅₀ values are calculated from dose-response curves. Alternatively, SREBP target gene expression (e.g., PCSK9, HMGCR) is measured by qRT-PCR or Western blot following Nicodicosapent treatment. For niacin receptor (GPR109A) binding assays, standard radioligand binding studies can be performed, but this is not the primary mechanism of action. Each concentration is tested in triplicate, and experiments are repeated at least three times.
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| Cell Assay |
In vitro cell-based assays for Nicodicosapent are performed using hepatocyte cell lines such as HepG2 or primary human hepatocytes. A typical protocol: cells are seeded in 96-well or 24-well plates at 50,000-100,000 cells/well and cultured in serum-containing medium for 24 hours. Cells are then serum-starved for 4-6 hours and treated with Nicodicosapent at concentrations ranging from 0.1 to 100 μM for 16-24 hours. Lipid metabolism endpoints include: intracellular cholesterol and triglyceride levels (measured by enzymatic assays or Oil Red O staining), PCSK9 secretion (measured by ELISA of culture media), HMG-CoA reductase activity (measured by enzyme assay), and expression of SREBP target genes (measured by qRT-PCR or Western blot). Cell viability is assessed using MTT or CellTiter-Glo assays to ensure that observed effects are not due to cytotoxicity. Each condition is tested in triplicate, and experiments are repeated at least three times.
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| Animal Protocol |
In vivo animal studies for Nicodicosapent have been conducted in rodent models of hyperlipidemia. A typical protocol: male C57BL/6 mice or Syrian hamsters are fed a high-fat diet for 2-4 weeks to induce hyperlipidemia. Animals are then administered Nicodicosapent via oral gavage at doses of 10-100 mg/kg, daily for 2-4 weeks. Blood samples are collected at baseline and at regular intervals for lipid profile analysis (total cholesterol, triglycerides, LDL-C, HDL-C). PCSK9 levels are measured in plasma by ELISA. At study termination, liver tissues are harvested for histopathological examination (H&E and Oil Red O staining) and for analysis of SREBP target gene expression by qRT-PCR or Western blot. Efficacy is assessed by comparing lipid levels and hepatic steatosis between treatment and vehicle control groups. The compound has also been evaluated in clinical trials.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Nicodicosapent have been evaluated in preclinical and clinical studies. The compound is administered orally and has demonstrated oral bioavailability. It is soluble in DMSO (≥60 mg/mL). Following oral administration, Nicodicosapent is absorbed and reaches therapeutic concentrations in the systemic circulation. The compound is metabolized, likely via hydrolysis of the amide bond to release EPA and niacin, which may contribute to its pharmacological effects. The half-life, volume of distribution, and clearance have been evaluated in preclinical models and in clinical trials. The compound's pharmacokinetic profile supports once-daily dosing in clinical studies. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, AUC, t₁/₂) have been reported in clinical trial publications. The compound is stable under recommended storage conditions (powder at -20°C for 3 years; in solvent at -80°C for 6 months).
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| Toxicity/Toxicokinetics |
Pharmacokinetic properties of Nicodicosapent have been evaluated in preclinical and clinical studies. The compound is administered orally and has demonstrated oral bioavailability. It is soluble in DMSO (≥60 mg/mL). Following oral administration, Nicodicosapent is absorbed and reaches therapeutic concentrations in the systemic circulation. The compound is metabolized, likely via hydrolysis of the amide bond to release EPA and niacin, which may contribute to its pharmacological effects. The half-life, volume of distribution, and clearance have been evaluated in preclinical models and in clinical trials. The compound's pharmacokinetic profile supports once-daily dosing in clinical studies. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, AUC, t₁/₂) have been reported in clinical trial publications. The compound is stable under recommended storage conditions (powder at -20°C for 3 years; in solvent at -80°C for 6 months).
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| References | |
| Additional Infomation |
Toxicological data for Nicodicosapent have been evaluated in preclinical safety studies supporting its clinical development. In animal studies, the compound has been generally well-tolerated at therapeutic doses. Common adverse effects may include gastrointestinal disturbances, flushing (due to the niacin moiety), and potential hepatotoxicity at high doses. The compound is currently in Phase 2 clinical trials, and safety data from these studies are being collected. Standard laboratory safety precautions should be followed when handling Nicodicosapent: use of personal protective equipment (gloves, safety goggles, lab coat) and handling in a well-ventilated fume hood. The compound should be stored at -20°C for long-term stability and at 4°C for short-term storage. Researchers should consult the safety data sheet (SDS) before handling.
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| Exact Mass |
449.304
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| CAS # |
1269181-69-2
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| PubChem CID |
50991753
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
677.5±55.0 °C at 760 mmHg
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| Flash Point |
363.5±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.540
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| LogP |
5.65
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
33
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| Complexity |
662
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCC(=O)NCCNC(=O)C1=CN=CC=C1
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| InChi Key |
YYQALOWPCKMFDQ-JLNKQSITSA-N
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| InChi Code |
InChI=1S/C28H39N3O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-21-27(32)30-23-24-31-28(33)26-20-19-22-29-25-26/h3-4,6-7,9-10,12-13,15-16,19-20,22,25H,2,5,8,11,14,17-18,21,23-24H2,1H3,(H,30,32)(H,31,33)/b4-3-,7-6-,10-9-,13-12-,16-15-
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| Chemical Name |
N-[2-[[(5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoyl]amino]ethyl]pyridine-3-carboxamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~222.41 mM)
Ethanol : ~3.33 mg/mL (~7.41 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.75 mg/mL (8.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 37.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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