| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
sphingosine-1-phosphate receptor[1]
Targets sphingosine-1-phosphate (S1P) receptors, likely S1PR1 and potentially S1PR5, as an agonist. By binding to S1P receptors on lymphocytes, Zectivimod induces receptor internalization and degradation, functionally antagonizing S1P signaling and preventing lymphocyte egress from secondary lymphoid organs. |
|---|---|
| ln Vitro |
In vitro, Zectivimod activates S1P receptors, leading to Gi-dependent signaling, including inhibition of adenylate cyclase, ERK1/2 phosphorylation, and actin cytoskeleton rearrangement in lymphocytes and endothelial cells. As an S1P receptor agonist, it functionally antagonizes lymphocyte chemotaxis toward S1P gradients. Zectivimod suppresses pro-inflammatory cytokine production from activated immune cells.
|
| ln Vivo |
Agonist for the sphingosine-1-phosphate receptor
In animal models of autoimmune diseases (e.g., experimental autoimmune encephalomyelitis [EAE], collagen-induced arthritis), Zectivimod reduces disease severity, peripheral lymphocyte counts, and inflammatory lesion formation. It suppresses immune cell infiltration into target organs, helping to restore immune balance without causing broad immunosuppression. Efficacy has been demonstrated in rat and mouse models. |
| Enzyme Assay |
Cell-free GTPgammaS binding assays are performed using membranes from CHO cells expressing human S1PR1 or S1PR5. Membranes (10 microg/well) are incubated with [3⁵S]GTPgammaS (0.1 nM), GDP (10 microM), and increasing concentrations of Zectivimod (0.01 nM-10 microM) in assay buffer for 60 min at 30degC. Bound radioactivity is separated by filtration through GF/B filters and quantified by scintillation counting to determine EC50 values.
|
| Cell Assay |
Human peripheral blood mononuclear cells (PBMCs) are isolated from fresh blood by Ficoll-Paque density gradient centrifugation. Cells are treated with Zectivimod (0.1-1000 nM) for 30 min at 37degC, then chemotaxis toward an S1P gradient (100 nM) is measured using a 5-microm pore Transwell plate for 2-4 h. Migrated cells in the lower chamber are counted by flow cytometry or using a fluorescent cell tracker dye.
|
| Animal Protocol |
In mouse EAE models (MOG35-55 peptide-induced), animals are immunized on day 0 and receive oral Zectivimod (0.1-1 mg/kg) daily for 21 days. Clinical scores (0-5 scale) and body weight are recorded daily. On day 21, spinal cords and brains are harvested for histology (H&E and Luxol fast blue staining), and inflammatory cell infiltration and demyelination are scored. Blood is collected for lymphocyte count analysis.
|
| ADME/Pharmacokinetics |
Detailed PK data for Zectivimod is not publicly available. As an S1P receptor agonist based on KRP-203, it is expected to have good oral bioavailability and a plasma half-life suitable for once-daily dosing in animal models. Its chemical formula is C2₈H31Cl2N3O3, MW 528.47.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for Zectivimod is not available in public sources. As an S1P receptor agonist, potential safety concerns may include first-dose bradycardia (heart rate reduction), macular edema, respiratory effects, and lymphopenia, similar to other compounds in this class (e.g., fingolimod). Standard toxicity assessments would be required for therapeutic development.
|
| References | |
| Additional Infomation |
Zectivimod is a small molecule drug. The INN prefix "-imod" in its name indicates that Zectivimod is an immunomodulator with both excitatory/inhibitory and excitatory effects. The monoisotope molecular weight of Zectivimod is 527.17 Da.
Zectivimod (KRP-203) is a research chemical not approved for clinical use. It is an S1P receptor agonist under investigation for autoimmune diseases, chronic inflammatory diseases, and immunoregulatory disorders. Zectivimod modulates lymphocyte trafficking by targeting S1P receptors. It is a member of the class of S1PR modulators that includes fingolimod, ozanimod, and siponimod. |
| Molecular Formula |
C28H31CL2N3O3
|
|---|---|
| Molecular Weight |
528.47004532814
|
| Exact Mass |
527.174
|
| CAS # |
1623066-63-6
|
| PubChem CID |
90356307
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
36
|
| Complexity |
816
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C2C=CC(=CC=2CCC=1CN1CCC(C(=O)O)CC1)OCC1C=CC2=C(C(=NN2C(C)C)Cl)C=1
|
| InChi Key |
XKKXISSRVOVRGI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C28H31Cl2N3O3/c1-17(2)33-25-8-3-18(13-24(25)27(30)31-33)16-36-22-6-7-23-20(14-22)4-5-21(26(23)29)15-32-11-9-19(10-12-32)28(34)35/h3,6-8,13-14,17,19H,4-5,9-12,15-16H2,1-2H3,(H,34,35)
|
| Chemical Name |
1-[[1-chloro-6-[(3-chloro-1-propan-2-ylindazol-5-yl)methoxy]-3,4-dihydronaphthalen-2-yl]methyl]piperidine-4-carboxylic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 100 mg/mL (189.23 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.73 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (4.73 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 25.0 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: ≥ 2.5 mg/mL (4.73 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 | 1.8923 mL | 9.4613 mL | 18.9226 mL | |
| 5 mM | 0.3785 mL | 1.8923 mL | 3.7845 mL | |
| 10 mM | 0.1892 mL | 0.9461 mL | 1.8923 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
