| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
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| Targets |
XT2 specifically targets NF-kappaB-inducing kinase (NIK), a serine/threonine kinase that serves as a central regulator of the non-canonical NF-kappaB signaling pathway. By inhibiting NIK activity, it blocks the downstream activation of NF-kappaB, a transcription factor critical for immune responses, inflammation, and cell survival.
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| ln Vitro |
XT2 inhibits NIK kinase activity with an IC50 of 9.1 nM in biochemical assays, representing about 1.7-fold greater potency than the comparator inhibitor B022 (IC50 of 15.1 nM). It potently suppresses NIK-driven gene expression in primary hepatocytes, demonstrating strong target engagement at the cellular level.
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| ln Vivo |
In a CCl4-induced acute liver injury model, XT2 significantly reduces the upregulation of ALT, a key biomarker of liver damage. It also reduces immune cell infiltration into damaged liver tissue, highlighting its anti-inflammatory effects in vivo. It is orally bioavailable in murine models, enabling chronic dosing.
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| Enzyme Assay |
For cell-free kinase assays, NIK enzyme (0.1-1 nM) is incubated with various concentrations of XT2 (0-100 nM) in a kinase buffer (50 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT) and 10 uM ATP. After 1 hour at room temperature, the reaction is stopped, and the remaining ATP is quantified using a Kinase-Glo Luminescent Kit. The IC50 value is calculated from the luminescence signal.
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| Cell Assay |
To validate cellular activity, primary hepatocytes or HEK293T cells are transfected with NIK. Cells are treated with XT2 (0.01-1 uM) for 4-24 hours. After treatment, cells are lysed and RNA is isolated. The expression of NIK-driven genes (e.g., CXCL1, CXCL2) is quantified via qRT-PCR. Protein levels of phosphorylated p100 (a marker of NIK activity) are measured by Western blot to confirm target engagement.
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| Animal Protocol |
In a murine model of acute liver injury, XT2 is administered orally at doses of 10-30 mg/kg. One hour post-administration, liver injury is induced by intraperitoneal injection of CCl4 (10 uL/kg in corn oil). After 24 hours, blood is collected to measure ALT/AST levels via colorimetric assays. Liver tissues are harvested for histology (H&E staining) and immunostaining to assess immune cell infiltration (e.g., F4/80 for macrophages).
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| ADME/Pharmacokinetics |
XT2 is orally bioavailable with moderate systemic exposure in murine models. The compound is soluble in DMSO and can be formulated for in vivo administration. The presence of a chiral center in its structure may impact its metabolic stability. Its terminal alkyne group allows it to serve as a click chemistry reagent.
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| Toxicity/Toxicokinetics |
XT2 is considered a research-grade chemical. Specific toxicological data such as maximum tolerated dose (MTD) is not widely published. However, as an inhibitor of NIK, its effects are primarily studied in the context of inflammation and liver disease. Standard safety precautions for handling kinase inhibitors should be followed.
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| Additional Infomation |
XT2 is a promising preclinical candidate for treating liver inflammatory diseases. Its unique structural feature as a click chemistry reagent makes it highly versatile for bioconjugation and probe development. It is still in the research phase and not approved for clinical use.
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| Molecular Formula |
C19H14FN5OS
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|---|---|
| Molecular Weight |
379.410765171051
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| Exact Mass |
379.09
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| CAS # |
2582816-37-1
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| PubChem CID |
155517858
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
27
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| Complexity |
611
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@](C#CC1=CC(=C(C=C1)F)C2=CNC3=CN=C(N=C23)N)(C4=NC=CS4)O
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| InChi Key |
NFAPIBSJICIXGB-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C19H14FN5OS/c1-19(26,17-22-6-7-27-17)5-4-11-2-3-14(20)12(8-11)13-9-23-15-10-24-18(21)25-16(13)15/h2-3,6-10,23,26H,1H3,(H2,21,24,25)/t19-/m1/s1
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| Chemical Name |
(2R)-4-[3-(2-amino-5H-pyrrolo[3,2-d]pyrimidin-7-yl)-4-fluorophenyl]-2-(1,3-thiazol-2-yl)but-3-yn-2-ol
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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 : ~50 mg/mL (~131.78 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 | 2.6357 mL | 13.1784 mL | 26.3567 mL | |
| 5 mM | 0.5271 mL | 2.6357 mL | 5.2713 mL | |
| 10 mM | 0.2636 mL | 1.3178 mL | 2.6357 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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