| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
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| Targets |
Lorpucitinib targets the Janus kinase (JAK) family of intracellular tyrosine kinases, which are key mediators of cytokine signaling through the JAK-STAT pathway. The compound inhibits all four human JAK isoforms (JAK1, JAK2, JAK3, TYK2), with the strongest inhibitory activity against JAK1/JAK3 and JAK1/TYK2 heterodimers. By inhibiting JAKs, lorpucitinib blocks the phosphorylation and activation of STAT proteins, reducing the production of inflammatory cytokines. The compound's enteric selectivity is designed to provide local efficacy in the gastrointestinal tract while minimizing systemic exposure.
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| ln Vitro |
In vitro, lorpucitinib demonstrates potent inhibition of JAK kinases and JAK/STAT signaling. The compound inhibits JAK-mediated phosphorylation of STAT proteins in cell-based assays. Lorpucitinib reduces the levels of inflammatory biomarkers in cell culture supernatants. The compound's enteric selectivity is assessed by measuring its permeability and efflux in intestinal epithelial cell models. Lorpucitinib shows good selectivity for JAKs over other kinases, contributing to its favorable safety profile.
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| ln Vivo |
In vivo, lorpucitinib demonstrates anti-inflammatory activity in preclinical models. The compound reduces serum levels of inflammatory biomarkers, indicating systemic anti-inflammatory effects. Lorpucitinib's enteric selectivity is intended to provide local efficacy in the gastrointestinal tract while minimizing systemic side effects. The compound has been evaluated in animal models of inflammatory bowel disease and other gastrointestinal inflammatory disorders.
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| Enzyme Assay |
Lorpucitinib's inhibition of JAK kinases is assessed using biochemical kinase assays. Recombinant JAK1, JAK2, JAK3, and TYK2 are incubated with the test compound, ATP, and a peptide substrate; phosphorylation of the substrate is detected using HTRF or luminescence-based methods. IC50 values are calculated from dose-response curves. Selectivity for JAK heterodimers (JAK1/JAK3, JAK1/TYK2) over JAK homodimers is assessed using appropriate assay formats. These assays provide quantitative information on the potency and selectivity of lorpucitinib.
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| Cell Assay |
Lorpucitinib is tested on cultured immune cells and intestinal epithelial cells. Cells are stimulated with cytokines in the presence or absence of lorpucitinib; STAT phosphorylation is assessed by flow cytometry or Western blot; cytokine production is measured by ELISA; cell proliferation is assessed by thymidine incorporation or CFSE dilution. Intestinal permeability and efflux are assessed using Caco-2 or MDCK cell models. These cell-based assays demonstrate the mechanism of action and enteric selectivity of lorpucitinib.
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| Animal Protocol |
Lorpucitinib is evaluated in animal models of inflammatory bowel disease and other gastrointestinal inflammatory disorders. In these models, lorpucitinib is administered orally; disease activity, histological inflammation, and inflammatory cytokine levels are assessed. Drug concentrations in plasma and intestinal tissue are measured to confirm enteric selectivity. These in vivo studies provide evidence for the efficacy and safety of lorpucitinib.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies of lorpucitinib have been conducted in preclinical species and humans. Lorpucitinib is orally bioavailable, with good oral bioavailability. The compound's enteric selectivity results in high concentrations in intestinal tissue and low systemic exposure. This pharmacokinetic profile is intended to minimize systemic side effects while providing local efficacy in the gastrointestinal tract.
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| Toxicity/Toxicokinetics |
In clinical trials, lorpucitinib has been generally well-tolerated. The enteric selectivity of the compound is intended to minimize the systemic side effects associated with JAK inhibitors, such as infections and hematologic abnormalities. Common adverse effects observed in clinical trials include gastrointestinal disturbances, which are consistent with the compound's local activity in the gut.
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| References | |
| Additional Infomation |
Loptinib is a highly bioavailable, orally bioavailable pan-Janus kinase (JAK) inhibitor with potential immunomodulatory and anti-inflammatory activities. After oral administration, loptinib acts in the gastrointestinal tract, targeting and binding to JAK, inhibiting its activity, thereby blocking the JAK-STAT signaling pathway and phosphorylation of STAT proteins. This may inhibit the release of pro-inflammatory cytokines and chemokines, alleviating inflammatory responses and preventing inflammation-induced damage. The Janus kinase family is a class of non-receptor tyrosine kinases, including tyrosine protein kinases JAK1, JAK2, JAK3, and TYK2, which play crucial roles in cytokine signaling and inflammation.
Lorpucitinib (JNJ-64251330) is an orally bioavailable pan-JAK inhibitor with good enteric selectivity and safety. The compound inhibits all four human JAKs, with the strongest inhibitory activity against JAK1/JAK3 and JAK1/TYK2 heterodimers. Lorpucitinib is being developed for the treatment of gastrointestinal inflammatory disorders, including familial adenomatous polyposis and inflammatory bowel diseases. The compound's enteric selectivity is intended to provide local efficacy in the gastrointestinal tract while minimizing systemic exposure and side effects. Lorpucitinib represents a promising new therapy for gastrointestinal inflammatory conditions. |
| Molecular Formula |
C22H28N6O2
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|---|---|
| Molecular Weight |
408.4967
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| Exact Mass |
408.227
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| CAS # |
2230282-02-5
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| PubChem CID |
134611548
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.691
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| LogP |
-0.82
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
30
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| Complexity |
668
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NJKMSBSVJSQUBU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H28N6O2/c1-22(2,30)13-26-19(29)11-18-27-17-12-25-21-16(8-10-24-21)20(17)28(18)15-5-3-14(4-6-15)7-9-23/h8,10,12,14-15,30H,3-7,11,13H2,1-2H3,(H,24,25)(H,26,29)
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| Chemical Name |
2-[3-[4-(cyanomethyl)cyclohexyl]-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaen-4-yl]-N-(2-hydroxy-2-methylpropyl)acetamide
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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 : ~250 mg/mL (~612.00 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.09 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 (5.09 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.09 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4480 mL | 12.2399 mL | 24.4798 mL | |
| 5 mM | 0.4896 mL | 2.4480 mL | 4.8960 mL | |
| 10 mM | 0.2448 mL | 1.2240 mL | 2.4480 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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