| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 100mg |
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| 250mg | |||
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| Targets |
Stearoyl‑CoA desaturase‑1 (SCD1). XEN723 exhibited a mouse SCD1 IC₅₀ = 6 nM and a human HepG2 cell‑based SCD1 IC₅₀ = 10 nM. [1]
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| ln Vitro |
Stearoyl-CoA desaturase (SCD1) is well inhibited by XEN723, a new and strong thiazolyl imidazolinone inhibitor, with IC50 values in mouse and HepG2 cells of 45 and 524 nM, respectively. XEN723 outperformed the initial high-throughput screening (HTS) hit in terms of SCD1 in vitro potency, increasing it by over 560-fold [1].
XEN723 showed potent inhibition of mouse SCD1 with an IC₅₀ of 6 nM in a mouse liver microsomal assay. In a human HepG2 cell‑based assay, it inhibited human SCD1 with an IC₅₀ of 10 nM. The compound displayed improved metabolic stability compared to analogue 19, with 67% of the compound remaining after a 30‑min incubation with 0.5 mg/mL rat liver microsomes. Overall, XEN723 achieved a more than 560‑fold increase in in vitro potency relative to the original HTS hit. [1] |
| ln Vivo |
In an acute Lewis rat model, oral administration of XEN723 at 5 mg/kg reduced the plasma C16:1/C16:0 triglyceride desaturation index by 59% at 4 h post‑dose (p < 0.001 vs. vehicle). In a dose‑response study (0.5–10 mg/kg, oral), XEN723 produced a clear dose‑related reduction in plasma triglyceride desaturation index, with an estimated ED₅₀ of 4.5 mg/kg. In a tolerability study, female Sprague‑Dawley rats dosed orally at 100 mg/kg once daily for ten days began to show mild eye symptoms on Day 3 and a dry skin phenotype on Day 4; these clinical signs (associated with SCD1 inhibition in harderian and sebaceous glands) progressively worsened throughout the study. [1]
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| Enzyme Assay |
The inhibitory activity of XEN723 against mouse SCD1 was assessed using a mouse liver microsomal assay. The exact protocol was not detailed in the paper; however, IC₅₀ values were determined from concentration‑response curves. No activity against delta‑5 desaturase (D5D) or delta‑6 desaturase (D6D) was observed at 10 μM for compounds with cell‑based SCD1 IC₅₀ < 100 nM, implying that XEN723 is selective for SCD1 over these related desaturases. [1]
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| Cell Assay |
Human SCD1 cellular potency was evaluated using a HepG2 cell‑based assay. This assay employed radiolabeled fatty acids to measure substrate/product ratios; specifically, radiolabeled stearic acid was used as the substrate to assess SCD1 activity. XEN723 yielded an IC₅₀ of 10 nM in this system. No further details on cell culture conditions or incubation times were provided. [1]
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| Animal Protocol |
- Acute pharmacodynamic model: Male Lewis rats were maintained on a high‑carbohydrate diet for one week prior to dosing. XEN723 was formulated in 1% carboxymethyl cellulose (low viscosity) : 0.2% Tween 20 : 98.8% water and administered orally at a volume of 3 mL/kg. Animals received a single dose of 5 mg/kg (for efficacy comparison) or doses ranging from 0.5 to 10 mg/kg (for dose‑response). Plasma samples were collected 4 hours after dosing. [1]
- Tolerability study: Female Sprague‑Dawley rats were dosed orally once daily with XEN723 at 100 mg/kg for ten consecutive days. Clinical signs (red eyes, hair loss, dry skin) were assessed daily. At the end of the study, plasma samples were collected for pharmacokinetic analysis. [1] |
| ADME/Pharmacokinetics |
- XEN723 exhibited moderate metabolic stability in vitro: 67% of the compound remained after a 30‑min incubation with 0.5 mg/mL rat liver microsomes. [1]
- In the tolerability study (100 mg/kg/day oral for 10 days in female rats), plasma exposure was relatively high: Cₘₐₓ = 6 μM and AUC₀‑₂₄ₕ = 78 μM·h. [1] |
| Toxicity/Toxicokinetics |
In a 10‑day oral tolerability study in female Sprague‑Dawley rats at 100 mg/kg/day, XEN723 caused adverse effects consistent with SCD1 inhibition. Animals started showing mild eye symptoms on Day 3 and dry skin on Day 4. These clinical signs (red eyes, hair loss, dry skin) progressively worsened over the study duration, indicating that prolonged systemic exposure and SCD1 inhibition in tissues such as skin and eye glands lead to severe side effects. [1]
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| References | |
| Additional Infomation |
XEN723 was developed as a potential treatment for metabolic diseases (e.g., obesity, insulin resistance, dyslipidemia) based on the known beneficial metabolic phenotype of SCD1 knockout mice and antisense oligonucleotide‑treated animals. Despite its robust in vitro and in vivo pharmacodynamic effects, the observed adverse effects (eye and skin toxicities) in rats suggest that selective tissue distribution or reduced systemic exposure would be necessary to improve the therapeutic index for clinical development. [1]
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| Molecular Formula |
C21H20FN5O2S
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|---|---|
| Molecular Weight |
425.479206085205
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| Exact Mass |
425.132
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| CAS # |
1072803-08-7
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| PubChem CID |
25095149
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| Appearance |
White to off-white solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
618
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S1C(C(NCC2=CC=CN=C2)=O)=C(C)N=C1N1C(=O)N(CC2=CC=C(F)C=C2)CC1
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| InChi Key |
OVFKEMNMAWPWAV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20FN5O2S/c1-14-18(19(28)24-12-16-3-2-8-23-11-16)30-20(25-14)27-10-9-26(21(27)29)13-15-4-6-17(22)7-5-15/h2-8,11H,9-10,12-13H2,1H3,(H,24,28)
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| Chemical Name |
2-[3-[(4-fluorophenyl)methyl]-2-oxoimidazolidin-1-yl]-4-methyl-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-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: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 (~235.03 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3503 mL | 11.7514 mL | 23.5029 mL | |
| 5 mM | 0.4701 mL | 2.3503 mL | 4.7006 mL | |
| 10 mM | 0.2350 mL | 1.1751 mL | 2.3503 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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