ZJCK-6-72
ZJCK-6-72 is a potent, orally effective DYRK1A inhibitor that crosses the blood-brain barrier, with an IC50 of 8.64 nM. ZJCK-6-72 binds to the hinge region of the ATP pocket of DYRK1A and reduces P-gp efflux, thereby blocking the activation of NF-κB and the NLRP3 inflammasome, and significantly downregulating pro-inflammatory cytokines such as TNF-α and IL-6, NO levels, and Pyroptosis. ZJCK-6-72 can be used for research on Alzheimer's disease.
For research use only. We do not sell to patients.
- CAS No.: 3135322-96-9
- Formula: C26H23N5O
- Molecular Weight:421.49
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
DYRK1A 8.64 nM (IC50) |
DYRK1B 15.10 nM (IC50) |
DYRK2 145.30 nM (IC50) |
IL-6 |
TNF-α |
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| BV-2 | IC50 |
>20 μM
|
Cytotoxicity against BV-2 microglial cells assessed by MTT assay after 4 hrs incubation.
Cytotoxicity against BV-2 microglial cells assessed by MTT assay after 4 hrs incubation.
|
acs.jmedchem.6c01681 |
In Vitro
ZJCK-6-72 (5 μM; pretreatment for 1 h, LPS stimulation for 6 h) inhibits LPS-induced TNF-α, IL-6, IL-1β, and MCP-1 mRNA expression in BV-2 microglia[1].
ZJCK-6-72 (0.1-30 μM; pretreatment for 1 h, LPS stimulation for 2-6 h) significantly inhibits TNF-α (EC50 = 0.71 μM) and IL-6 (EC50 = 0.61 μM) release in LPS-activated BV-2 microglia and maintains very low cytotoxicity, with inhibition rates of 83.94% and 94.65%, respectively, at a concentration of 5 μM[1].
ZJCK-6-72 (5 μM; pretreatment for 1 h, LPS induction for 24 h followed by ATP induction for 2 h) dose-dependently inhibits NLRP3 inflammasome-mediated IL-1β release (EC50 = 0.68 μM) and reduces lactate dehydrogenase (LDH) release in LPS- and ATP (HY-B2176) co-stimulated BV-2 cells, demonstrating cytoprotective and anti-pyroptotic effects[1].
ZJCK-6-72 (24 h) inhibits LPS (HY-D1056)-induced NO production in BV-2 microglia, with an EC50 of 2.71 μM[1].
ZJCK-6-72 (60 min) inhibits purified DYRK1A with an IC50 of 8.64 nM[1].
ZJCK-6-72 (0.5 μM; 60 min) most potently inhibits CLK4, CLK1, DYRK1A, and DYRK1B in kinase profiling assays, with IC50 values of 3.62, 11.67, 9.52, and 15.10 nM[1].
ZJCK-6-72 (0.001-30 μM; 3 h) binds and stabilizes DYRK1A in BV-2 cells in a concentration-dependent manner, with an IC50 of 3.63 nM[1].
ZJCK-6-72 exhibits low cytotoxicity against BV-2 microglia, with an IC50 >20 μM[1].
ZJCK-6-72 (5 μM; 90 min) has a low P-gp efflux risk in MDCK-MDR1 cells, with an ER of 0.38; it exhibits a moderate BCRP efflux risk in MDCK-BCRP cells, with an ER of 5.66[1].
ZJCK-6-72 (60 min) inhibits DYRK1A (IC50 = 9.52 nM), DYRK1B (IC50 = 15.10 nM), CLK1 (IC50 = 11.67 nM), CLK4 (IC50 = 3.62 nM), and DYRK2 (IC50 = 145.30 nM) in a cell-free ADP-Glo kinase assay[1].
ZJCK-6-72 (5 μM) significantly reverses LPS-induced morphological changes in LPS-stimulated BV-2 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:BV-2 microglial cells
-
Concentration:5 μM
-
Incubation Time:1 h (pre-incubation); 6 h (LPS)
-
Result:Showed comparable efficacy to dexamethasone in inhibiting TNF-α, IL-6, and IL-1β mRNA overexpression.
-
Cell Line:BV-2 microglial cells
-
Concentration:5 μM
-
Incubation Time:1 h (pre-incubation); 2 h (LPS);
-
Result:Inhibited LPS-induced TNF-α release with an inhibition rate of 83.94%.
-
Cell Line:BV-2 microglial cells
-
Concentration:5 μM
-
Incubation Time:1 h (pre-incubation); 6 h (LPS);
-
Result:Inhibited LPS-induced IL-6 release with an inhibition rate of 94.65%.
Parmacokinetics
| Species | Dose | Route | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | T1/2 | Cmax | F | CLz | Vz |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 4 mg/kg | i.v. | 1005.15 ng·h/mL | 1020.44 ng·h/mL | 1.38 h | 1.51 h | 1.17 h | 721.77 ng/mL | / | 3.93 L/h/kg | 6.71 L/kg |
| Rat[1] | 20 mg/kg | p.o. | 5223.05 ng·h/mL | 6185.44 ng·h/mL | 3.30 h | 4.34 h | 3.11 h | 1012.90 ng/mL | ∼100 % | / | / |
| Mice[1] | 2 mg/kg | i.v. | 1795.38 ng·h/mL | 1801.47 ng·h/mL | 3.21 h | 3.39 h | 2.40 h | 495.33 ng/mL | / | 1.12 L/h/kg | 3.97 L/kg |
| Mice[1] | 10 mg/kg | p.o. | 6418.08 ng·h/mL | 6645.18 ng·h/mL | 5.97 h | 6.85 h | 4.74 h | 954.73 ng/mL | 71.50 % | / | / |
In Vivo
ZJCK-6-72 (2.5-10 mg/kg; p.o.; once daily; 7 days of pretreatment, followed by 7 days in combination with LPS) alleviates LPS-induced neuroinflammation and neuronal damage in C57BL/6 mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (male, 20-25 g)[1]
-
Dosage:2.5 mg/kg; 5 mg/kg; 10 mg/kg
-
Administration:p.o.; once daily; 7 days before LPS and additional 7 days with LPS
-
Result:Significantly and dose-dependently alleviated the LPS-induced clinical illness scores and prevented excessive weight loss in mice.
Significantly mitigated the neuronal damage induced by LPS in the cerebral cortex and hippocampal dentate gyrus of mice.
Suppressed the mRNA overexpression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the cerebral cortex and hippocampus.
Reversed the LPS-induced overactivation and abnormal proliferation of microglia (Iba-1+) in the mouse brain.
Chemical Information
-
CAS No. 3135322-96-9
-
Molecular Weight 421.49
-
Formula C26H23N5O
-
SMILES
CC(C=C1)=NC2=C1C(C3=CC4=C(C=C3)N=CN=C4N5CCO[C@@H](C6=CC=CC=C6)C5)=CN2
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ZJCK-6-72 Related Classifications
HY-189843 Related Classifications
Powered by Bioz