| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
D5D-IN-326 selectively inhibits the delta-5 desaturase (D5D) enzyme, with no measurable activity against delta-6 desaturase (D6D) or delta-9 desaturase (D9D). Inhibition of D5D modulates the balance of LC-PUFAs, particularly the arachidonic acid and eicosapentaenoic acid pathways, which are involved in various metabolic and inflammatory signaling cascades. This selectivity makes it a valuable tool for dissecting the role of D5D in physiology.
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| ln Vitro |
In enzymatic and cellular studies, D5D-IN-326 is a selective and potent oral delta-5 desaturase (D5D) inhibitor, with IC50 values of 72 and 22 nM for rat and human D5D, respectively, and for D6D or D9D. Exercise has no impact [1].
In enzymatic and cell-based assays, D5D-IN-326 potently inhibits rat D5D with an IC50 of 72 nM and human D5D with an IC50 of 22 nM. It shows no inhibition of D6D or D9D up to 100 µM. In cellular assays using hepatocytes or adipocytes, the compound reduces the conversion of dihomo-γ-linolenic acid to arachidonic acid, altering the fatty acid profile and downstream eicosanoid production. |
| ln Vivo |
When given orally for six weeks, D5D-IN-326 (0.1, 1 and 10 mg/kg) progressively decreased body weight at the 10 mg/kg dose; however, in DIO mice, lesser doses were ineffective after six weeks of treatment [1]. Additionally, D5D-IN-326 (10 mg/kg, orally administered for 6 weeks) dramatically decreased the levels of Ccl2, Cd68, Adgre1, and Il6 gene expression, as well as the mRNA for epididymal Lep and Adipoq, which were significantly elevated in HFD DIO mice [1].
In diet-induced obese (DIO) C57BL/6J mice, oral administration of D5D-IN-326 at 10 mg/kg for six weeks reduced insulin resistance, decreased body weight, and lowered fasting glucose levels. The compound also significantly decreased the expression of inflammatory markers (Ccl2, Cd68, Adgre1, Il6) and adipose-associated genes (Lep, Adipoq). Lower doses (0.1 and 1 mg/kg) were ineffective, indicating a dose-dependent response. |
| Enzyme Assay |
In cell-free enzymatic assays, D5D activity is measured by incubating microsomal fractions containing human or rat D5D with a radiolabeled or deuterated substrate (e.g., dihomo-γ-linolenic acid). The reaction product (arachidonic acid) is quantified by gas chromatography-mass spectrometry (GC-MS) after lipid extraction. Inhibitor concentrations are varied to determine IC50 values. The assay is performed in Tris-HCl buffer with NADH as cofactor.
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| Cell Assay |
Cell-based assays typically involve culturing human hepatoma cells (e.g., HepG2) or primary mouse hepatocytes with various concentrations of D5D-IN-326 for 24-48 hours. Cells are then harvested, and total lipids are extracted and methylated. Fatty acid methyl esters are analyzed by GC-FID or GC-MS to measure the D5D activity index (product/substrate ratio). Gene expression of FADS1 and inflammatory cytokines is also measured by qPCR.
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| Animal Protocol |
For in vivo studies, male C57BL/6J mice are fed a high-fat diet (60% kcal from fat) for 12 weeks to induce obesity. Then, D5D-IN-326 is administered orally once daily at doses of 0.1, 1, or 10 mg/kg for 6 weeks. Body weight and food intake are recorded weekly. At the end, insulin tolerance tests and glucose tolerance tests are performed. Tissues (liver, adipose) are collected for gene expression and lipid analysis.
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| ADME/Pharmacokinetics |
D5D-IN-326 is orally bioavailable with good exposure in plasma and tissues. In DIO mice, oral administration at 10 mg/kg achieved sufficient concentrations to inhibit D5D in the liver and adipose tissue. The compound has a moderate half-life allowing once-daily dosing. Its pharmacokinetic profile supports its use in chronic metabolic studies. No specific human PK data is available.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for D5D-IN-326. In the DIO mouse study, the compound was well tolerated at 10 mg/kg for six weeks with no overt signs of toxicity, body weight loss (except fat reduction), or behavioral changes. Hepatic and renal function markers were not reported. As a metabolic inhibitor, it is considered a research chemical with potential off-target effects, but no acute toxicity data is published.
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| References | |
| Additional Infomation |
D5D-IN-326 is a selective, orally active inhibitor of delta-5 desaturase, with molecular formula C17H11F8N3O4 and molecular weight 473.27. It is also referred to as Compound-326. It is a research tool for studying the role of LC-PUFA biosynthesis in metabolic diseases. The compound is available for research purposes only and is not for human therapeutic use. It has been cited in high-impact journals for its effects on insulin resistance.
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| Molecular Formula |
C17H11F8N3O4
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| Molecular Weight |
473.274172067642
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| Exact Mass |
473.062
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| CAS # |
1236767-85-3
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| PubChem CID |
59416313
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| Appearance |
Pale purple to purple solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
32
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| Complexity |
829
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC(C(F)(F)F)(COC1=NC2=C(C(N1C1C=CC(=CC=1)OCC(F)(F)F)=O)CC(N2)=O)F
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| InChi Key |
NGUQGJZXDBRNOL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H11F8N3O4/c18-15(19,17(23,24)25)6-32-14-27-12-10(5-11(29)26-12)13(30)28(14)8-1-3-9(4-2-8)31-7-16(20,21)22/h1-4H,5-7H2,(H,26,29)
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| Chemical Name |
2-(2,2,3,3,3-pentafluoropropoxy)-3-[4-(2,2,2-trifluoroethoxy)phenyl]-5,7-dihydropyrrolo[2,3-d]pyrimidine-4,6-dione
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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 |
| 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 : ~125 mg/mL (~264.12 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.39 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 20.8 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: ≥ 2.08 mg/mL (4.39 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1130 mL | 10.5648 mL | 21.1296 mL | |
| 5 mM | 0.4226 mL | 2.1130 mL | 4.2259 mL | |
| 10 mM | 0.2113 mL | 1.0565 mL | 2.1130 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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