PROTAC JAK1/2 degrader-1
Based on 1 Customer Validation
PROTAC JAK1/2 degrader-1 is an orally active JAK1/JAK2 PROTAC degrader, with DC50 values of 1.4 μM and 0.92 μM against JAK1 and JAK2, respectively. PROTAC JAK1/2 degrader-1 triggers degradation via a CRBN- and proteasome-dependent pathway. PROTAC JAK1/2 degrader-1 inhibits the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). PROTAC JAK1/2 degrader-1 alleviates inflammatory responses and colon injury by inhibiting the JAK/STAT3 signaling pathway. PROTAC JAK1/2 degrader-1 can be used for the research of inflammatory bowel disease.
(Pink: JAK1 and JAK2 ligand (HY-179716); Blue: Cereblon ligand (HY-10984); Black: linker).
For research use only. We do not sell to patients.
- Purity: 99.47%
- Formula: C33H29N7O5
- Molecular Weight:603.63
-
Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
All PROTACs Isoforms
More
Biological Activity
|
JAK1 1.4 μM (DC50) |
JAK2 0.92 μM (DC50) |
IL-6 |
STAT3 |
TNF-α |
PROTAC JAK1/2 degrader-1 (compound A8) (3 μM; 1 h followed by 6 h LPS stimulation) degrades JAK1 protein in LPS-stimulated Raw 264.7 cells[1].
PROTAC JAK1/2 degrader-1 (0.469-60 μM; 24 h) shows no cytotoxicity in Raw 264.7 cells[1].
PROTAC JAK1/2 degrader-1 (0.47-60 μM) induces dose-dependent degradation of JAK1 in LPS-stimulated Raw 264.7 cells with a DC50 of 1.40 μM[1].
PROTAC JAK1/2 degrader-1 (1.5 μM; 3 μM MG132 (HY-13259)) mediates JAK1 degradation in Raw 264.7 cells via a proteasome-dependent pathway, as degradation is inhibited by MG132, and the separate warhead and E3 ligase ligand components do not induce degradation[1].
PROTAC JAK1/2 degrader-1 (0.47-60 μM) is a selective JAK1/2 degrader, dose-dependently degrading JAK2 with a DC50 of 0.92 μM while not affecting JAK3 or TYK2 levels at concentrations up to 60 μM in Raw 264.7 cells[1].
PROTAC JAK1/2 degrader-1 (0.469-60 μM; 24 h) suppresses NO production in LPS-stimulated Raw 264.7 cells in a dose-dependent manner, with significant inhibition starting at 0.469 μM[1].
PROTAC JAK1/2 degrader-1 (0.05-60 μM; 24 h) suppresses IL-6 and TNF-α secretion in LPS-stimulated Raw 264.7 cells with IC50 values of 12.89 μM and 17.17 μM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:Raw 264.7 cells
-
Concentration:3 μM
-
Incubation Time:1 h (compound); 6 h (LPS stimulation)
-
Result:Effectively degraded JAK1 protein levels in LPS-stimulated Raw 264.7 cells.
-
Cell Line:Raw 264.7 cells
-
Concentration:0.469-60 μM
-
Incubation Time:24 h
-
Result:Exhibited no cytotoxicity at all tested concentrations, with cell viability remaining comparable to control levels.
-
Cell Line:LPS-stimulated Raw 264.7 cells
-
Concentration:0.05-60 μM
-
Incubation Time:24 h
-
Result:Exhibited dose-dependent suppression of IL-6 and TNF-α secretion, with IC50 values of 12.89 μM for IL-6 and 17.17 μM for TNF-α.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (8 animals per group; DSS-induced colitis model)[1]
-
Dosage:10 mg/kg; 20 mg/kg; 40 mg/kg
-
Administration:p.o.; daily; 7 days
-
Result:Improved maintenance of body weight compared to the DSS-induced model group.
Reduced disease activity index (DAI) scores compared to the DSS-induced model group.
Restored colon length compared to the DSS-induced model group.
Decreased spleen index compared to the DSS-induced model group.
Alleviated colonic histopathological alterations including epithelial shedding, crypt damage, and inflammatory cell infiltration.
Restored goblet cell numbers and mucin production.
Restored tight junction protein (ZO-1, occludin) expression.
Reduced serum and colonic levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α.
Restored serum and colonic levels of anti-inflammatory cytokine IL-10.
Reduced total white blood cell, lymphocyte, monocyte, and neutrophil counts.
Attenuated colonic expression of myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS).
Downregulated colonic JAK1, JAK2, and IL-6 expression.
Inhibited STAT3 phosphorylation.
Reduced colonic p-STAT3, JAK1, and JAK2 expression.
Showed no histopathological changes in major organs (heart, liver, spleen, lung, kidney) at all tested doses.
Chemical Information
-
Appearance Solid
-
Molecular Weight 603.63
-
Formula C33H29N7O5
-
Color Light yellow to yellow
-
SMILES
O=C(NCCCNC1=CC=CC(C(N2C(CC3)C(NC3=O)=O)=O)=C1C2=O)C4=CC=C(C5=NC(NC6=CC=CC=C6)=NC=C5)C=C4
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 100 mg/mL (165.66 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
-
Data Sheet (284 KB)
-
SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
-
Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.6566 mL | 8.2832 mL | 16.5664 mL | 41.4161 mL |
| 5 mM | 0.3313 mL | 1.6566 mL | 3.3133 mL | 8.2832 mL | |
| 10 mM | 0.1657 mL | 0.8283 mL | 1.6566 mL | 4.1416 mL | |
| 15 mM | 0.1104 mL | 0.5522 mL | 1.1044 mL | 2.7611 mL | |
| 20 mM | 0.0828 mL | 0.4142 mL | 0.8283 mL | 2.0708 mL | |
| 25 mM | 0.0663 mL | 0.3313 mL | 0.6627 mL | 1.6566 mL | |
| 30 mM | 0.0552 mL | 0.2761 mL | 0.5522 mL | 1.3805 mL | |
| 40 mM | 0.0414 mL | 0.2071 mL | 0.4142 mL | 1.0354 mL | |
| 50 mM | 0.0331 mL | 0.1657 mL | 0.3313 mL | 0.8283 mL | |
| 60 mM | 0.0276 mL | 0.1381 mL | 0.2761 mL | 0.6903 mL | |
| 80 mM | 0.0207 mL | 0.1035 mL | 0.2071 mL | 0.5177 mL | |
| 100 mM | 0.0166 mL | 0.0828 mL | 0.1657 mL | 0.4142 mL |
PROTAC JAK1/2 degrader-1 Related Classifications
HY-179715 Related Classifications
Powered by Bioz