| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
IC50: 20.3 nM (Glucocorticoid recepto), 20.4 nM (Progesterone receptor ) and 79.9 nM (mineralocorticoid receptor)[1]
Glucocorticoid receptor (GR). As an agonist, (-)-ZK 216348 (or its active enantiomer) binds to the GR in the cytoplasm, leading to receptor translocation to the nucleus. There, it modulates gene expression: repressing pro-inflammatory transcription factors (transrepression) while having reduced activation of glucocorticoid response elements (transactivation). |
|---|---|
| ln Vitro |
ZK 216348 suppresses TNF-α and IL-12 in human peripheral blood mononuclear cells (PBMCs) at IC50 values of 89 nM and 52 nM, respectively[1]. The role of an active GR in ZK 216348's anti-inflammatory response is further studied in Caco-2 cells, where ZK 216348 suppresses the pro-inflammatory cytokine IL-8's TNF-α-induced expression[2].
(+)-ZK 216348 has an IC50 of 20.3 nM for the glucocorticoid receptor. It also shows some binding to progesterone (IC50 = 20.4 nM) and mineralocorticoid (IC50 = 79.9 nM) receptors. It shows anti-inflammatory activity comparable to prednisolone in HeLa cells (inhibition of TPA-induced collagenase). The (-)-enantiomer is significantly less active. |
| ln Vivo |
In both mice and rats, ZK 216348 therapy (subcutaneous injection; 1–30 mg/kg; 24 hours; NMRI mice and Wistar rats) prevents ear edema. ZK 216348 has a notably better side-effect profile when it comes to blood glucose rises, spleen involution, and, to a lesser extent, skin atrophy[1].
In murine models of acute inflammation (e.g., TPA-induced ear edema or carrageenan-induced paw edema), (+)-ZK 216348 shows potent anti-inflammatory activity for both systemic and topical application. Importantly, it shows no negative effects on intestinal epithelial migration or proliferation, suggesting reduced gastrointestinal toxicity compared to classical steroids. |
| Enzyme Assay |
Glucocorticoid receptor binding affinity is assessed using a radioligand competition binding assay. Cytosolic GR from rat or human cell lysates is incubated with [3H]-dexamethasone (1-5 nM) and varying concentrations of test compound for 2-24 hours at 4degC. Bound and free radioligand are separated by charcoal adsorption or filtration. Nonspecific binding is determined with excess unlabeled dexamethasone. IC50 values are calculated.
|
| Cell Assay |
HeLa cells are transfected with a luciferase reporter gene under the control of a glucocorticoid response element (GRE). Cells are treated with varying concentrations of test compound for 6-24 hours. Luciferase activity is measured to assess transactivation activity. For transrepression, cells are stimulated with TPA, and collagenase production is measured by ELISA. The ratio indicates selectivity.
|
| Animal Protocol |
For topical efficacy, the TPA-induced ear edema model in mice is used. TPA is applied to the right ear to induce inflammation. Test compound (-)-ZK 216348 or vehicle is applied topically or systemically (p.o. or i.p.). After 6 hours, ear punch biopsies are weighed, and inflammation is assessed by myeloperoxidase (MPO) activity and histological analysis of edema and neutrophil infiltration.
|
| ADME/Pharmacokinetics |
While detailed PK data for ZK 216348 is not extensively published as it is a research tool, steroidal and nonsteroidal GR agonists typically have good oral bioavailability (40-80%) and moderate half-lives. (+)-ZK 216348 is metabolized primarily in the liver, likely by CYP3A4. It distributes well to inflamed tissues, contributing to its efficacy in topical and systemic models.
|
| Toxicity/Toxicokinetics |
ZK 216348 was developed with the goal of reducing the classical steroid side effects: osteoporosis, diabetes/glucose intolerance, skin atrophy, and growth retardation. The compound showed significantly reduced transactivation-mediated effects. In studies of intestinal epithelial migration, (-)-ZK 216348 showed no negative effects, indicating a favorable GI safety profile.
|
| References |
|
| Additional Infomation |
ZK-209614 is a racemic mixture, ZK-216348 is a (+)- isomer, and ZK-216347 is a (-)- isomer; all are selective glucocorticoid receptor agonists; structures are described in the first source.
(+)-ZK 216348 is a research compound that demonstrated promise in preclinical models of inflammatory diseases, showing anti-inflammatory activity comparable to prednisolone but with a reduced side effect profile. It has not yet been approved by the FDA or other regulatory agencies for human use and is not currently in active clinical development to the best of public knowledge. It remains a valuable pharmacological tool. |
| Molecular Formula |
C24H23F3N2O5
|
|---|---|
| Molecular Weight |
476.45
|
| Exact Mass |
476.156
|
| Related CAS # |
ZK 216348;669073-68-1
|
| PubChem CID |
92293311
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
2
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
34
|
| Complexity |
845
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC1=NOC(=O)C2=C1C=C(C=C2)NC(=O)[C@](CC(C)(C)C3=CC=CC4=C3OCC4)(C(F)(F)F)O
|
| InChi Key |
VRZVKIJRJRBQJT-HSZRJFAPSA-N
|
| InChi Code |
InChI=1S/C24H23F3N2O5/c1-13-17-11-15(7-8-16(17)20(30)34-29-13)28-21(31)23(32,24(25,26)27)12-22(2,3)18-6-4-5-14-9-10-33-19(14)18/h4-8,11,32H,9-10,12H2,1-3H3,(H,28,31)/t23-/m1/s1
|
| Chemical Name |
(2R)-4-(2,3-dihydro-1-benzofuran-7-yl)-2-hydroxy-4-methyl-N-(4-methyl-1-oxo-2,3-benzoxazin-6-yl)-2-(trifluoromethyl)pentanamide
|
| 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 :~230 mg/mL (~482.74 mM)
|
|---|---|
| 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 | 2.0989 mL | 10.4943 mL | 20.9886 mL | |
| 5 mM | 0.4198 mL | 2.0989 mL | 4.1977 mL | |
| 10 mM | 0.2099 mL | 1.0494 mL | 2.0989 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
