| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
LUF6283 targets the hydroxycarboxylic acid receptor 2 (HCA2/GPR109A/HM74A), a G protein-coupled receptor that mediates the lipid-lowering effects of niacin. It acts as a partial agonist with a Ki of 0.55 μM in radioligand competitive binding assays. The compound shows biased signaling with a G protein EC₅₀ of 3.1 μM versus a pERK1/2 EC₅₀ of 0.32 μM (10-fold bias ratio).
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| ln Vitro |
In vitro, LUF6283 acts as an HCA2 partial agonist. It induces ERK1/2 phosphorylation with an EC₅₀ of 0.32 ± 0.06 μM. The compound stimulates [³⁵S]-GTPγS binding and increases phosphorylation of ERK in HEK293T cells expressing GPR109A/HCA2 receptors. It has a Ki of 0.55 μM in radioligand binding assays.
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| ln Vivo |
Apolipoprotein B (APOB) expression is dramatically reduced by LUF6283 (C57BL/6 mice, 400 mg/kg, oral gavage, once daily, for 4 weeks), while ATGL/HSL expression in adipose tissue is unaffected [1].
In vivo, LUF6283 has been studied in C57BL/6 mice. Oral administration (400 mg/kg, once daily for 4 weeks) leads to a reduction in apolipoprotein B (APOB) expression. The compound achieves the beneficial lipid-lowering effects of niacin without inducing skin flushing. LUF6283 reduces hepatic APOB expression by more than 40% without altering adipose lipolysis. |
| Enzyme Assay |
Non-cellular receptor binding assays for LUF6283 involve radioligand displacement using membrane preparations expressing the human HCA2 receptor. Membranes are incubated with a radiolabeled HCA2 ligand and varying concentrations of LUF6283. Bound radioactivity is measured by filtration and scintillation counting. Ki values are calculated from competition binding curves.
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| Cell Assay |
In vitro cellular experiments involve HEK293T cells expressing GPR109A/HCA2 receptors. Cells are treated with LUF6283 at various concentrations. ERK1/2 phosphorylation is measured by Western blot or immunoassay. [³⁵S]-GTPγS binding is measured to assess receptor activation. EC₅₀ values are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal studies involve C57BL/6 mice. LUF6283 is administered orally by gavage (400 mg/kg, once daily for 4 weeks). Lipid metabolism markers, including APOB expression, are measured. Flushing response is monitored to confirm the absence of this side effect.
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| ADME/Pharmacokinetics |
LUF6283 is orally bioavailable. It has a molecular weight of 168.19 g/mol and a molecular formula of C₈H₁₂N₂O₂. The compound is soluble in DMSO. Storage: powder at -20°C for 3 years; in solvent at -80°C for 1 year.
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| Toxicity/Toxicokinetics |
Specific toxicity data for LUF6283 is limited. The compound is designed to avoid the skin flushing side effect associated with niacin. As an HCA2 partial agonist, it is expected to have a favorable safety profile. The compound is for research purposes only and should be handled with appropriate safety precautions.
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| References | |
| Additional Infomation |
LUF6283 is a potent, orally active partial agonist of HCA2/GPR109A with a Ki of 0.55 μM. It achieves the lipid-lowering effects of niacin without causing skin flushing. The compound shows biased signaling with differential EC₅₀ values for G protein activation and ERK phosphorylation. This product is for research purposes only and is not for human therapeutic use.
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| Molecular Formula |
C8H12N2O2
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|---|---|
| Molecular Weight |
168.19308
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| Exact Mass |
168.09
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| CAS # |
92933-48-7
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| PubChem CID |
6485181
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| Appearance |
White to light yellow solid powder
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| LogP |
1.45
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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 |
4
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| Heavy Atom Count |
12
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| Complexity |
161
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(C1=NNC(CCCC)=C1)O
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| InChi Key |
ZJTXSGLJNBAMJS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H12N2O2/c1-2-3-4-6-5-7(8(11)12)10-9-6/h5H,2-4H2,1H3,(H,9,10)(H,11,12)
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| Chemical Name |
5-butyl-1H-pyrazole-3-carboxylic acid
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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, 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 (~594.6 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.86 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 DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (14.86 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 DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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 (14.86 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 DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.9457 mL | 29.7283 mL | 59.4566 mL | |
| 5 mM | 1.1891 mL | 5.9457 mL | 11.8913 mL | |
| 10 mM | 0.5946 mL | 2.9728 mL | 5.9457 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.
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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