PROTAC MNK1 degrader-1
Based on 1 Customer Validation
PROTAC MNK1 degrader-1 is a selective MNK1 PROTAC degrader with a DC50 of 11.92 nM, and a Dmax > 96% in MV4-11 cells. PROTAC MNK1 degrader-1 significantly reduces p-eIF4E (IC50: 22.07 nM), induces apoptosis, and arrests the cell cycle at the G1 phase. PROTAC MNK1 degrader-1 has potent antitumor activity. PROTAC MNK1 degrader-1 has robust antileukemic efficacy in MV4-11 xenograft mice model with acceptable drug safety.
(Pink: MNK1 ligand (HY-176429); Blue: Cereblon ligand (HY-A0003); Black: linker (HY-Y1139)).
For research use only. We do not sell to patients.
- Purity: 98.93%
- CAS No.: 3120743-91-8
- Formula: C35H38N6O6S
- Molecular Weight:670.78
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Storage:Powder -20°C, 3 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]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Bioactive Compound Library Max
HY-L181
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Bioactive Compound Library
HY-L001
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Apoptosis Compound Library
HY-L003
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Cell Cycle/DNA Damage Compound Library
HY-L004
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Immunology/Inflammation Compound Library
HY-L007
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MAPK Compound Library
HY-L010
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Anti-Cancer Compound Library
HY-L025
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Anti-Aging Compound Library
HY-L034
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Oxygen Sensing Compound Library
HY-L045
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PROTAC Library
HY-L151
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Highly Selective Inhibitors Library
HY-L158
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Highly Selective Activators Library
HY-L159
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Cell Death Library
HY-L162
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Multi-Target Compound Library
HY-L176
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MCE Bioactive Compound Library
HY-L001V
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Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
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High-Throughput Bioactive Compound Library
HY-L205
All PROTACs Isoforms
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Biological Activity
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MNK1 11.92 nM (DC50) |
eIF4 22.07 nM (IC50) |
PROTAC MNK1 degrader-1 (Compound P11-2) (0.001-10 μM, 24h) significantly enhances anti-proliferative activity in four cancer cell lines, with IC50 s of 0.045, 0.24, 0.61 and 2.06μM for MV4-11, MM.1S, MOLM-13, and MDA-MB-231 cells, respectively[1].
PROTAC MNK1 degrader-1 (300 nM, 1-24h) CRBN- and proteasome-dependently induces MNK1 degradation with a t1/2 of 3.64 h in MV4-11 cells[1].
PROTAC MNK1 degrader-1 (10-1000 nM, 24h) effectively inhibits tumor cell proliferation by selectively degrading MNK1 and reduces protein level of p-eIF4E (downstream factor) with an IC50 of 22.07 nM in MV4-11 cells[1].
PROTAC MNK1 degrader-1 has superior binding capacity on active pocket of CRBN and MNK1, with the linker forming a hydrogen bond with H353[1].
PROTAC MNK1 degrader-1 (30-300 nM, 24h) dose-dependently induces cell apoptosis (especially in late apoptosis) and arrests cell cycle in the G1 phase in MV4-11 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 cells
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Concentration:0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3 μM
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Incubation Time:1, 2, 4, 8, 16, 24 h
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Result:Dose-dependently reduced the protein levels of MNK1 with a DC50 of 11.92 nM and a Dmax > 96% in MV4-11 cells.
Rapidly degraded MNK1 at the dose of 300 nM, with a t1/2 of 3.64 h in MV4–11 cells.
Induced MNK1 degradation in a CRBN- and proteasome-dependent manner, while bortezomib significantly diminished the degradation in MV4-11 cells.
Selectively degraded MNK1 and reduced protein level of p-eIF4E with IC50 of 22.07 nM in MV4-11 cells.
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Cell Line:MOLM-13, MM.1S, MDA-MB-231 cells
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Concentration:MOLM-13 and MM.1S cells (0.01, 0.03, 0.1, 0.3, 1 μM), MDA-MB-231 cells (0.1, 0.3, 1, 3, 10 μM)
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Incubation Time:24 h
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Result:Dose-dependently reduced the protein levels of MNK1 in MOLM-13, MM.1S, and MDA-MB-231 cells, with a pronounced degradation effect in MM.1S cells.
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Cell Line:MV4-11 cells
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Concentration:30, 100, 300 nM
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Incubation Time:24 h
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Result:Dose-dependently induced apoptosis (especially in late apoptosis) with the total apoptotic percentage of the cell increased to 13.9, 27.8, and 70.7% in MV4-11 cells.
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Cell Line:MV4-11 cells
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Concentration:30, 100, 300 nM
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Incubation Time:24 h
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Result:Significantly increased the proportion of cells in the G1 phase and decreased the proportions in the S and G2 phases in a dose-dependent manner.
| Species | Dose | Route | AUC | T1/2 | Clearance (CL) | Plasma Concentration | Bioavailability | Tmax |
|---|---|---|---|---|---|---|---|---|
| Rat | 1 mg/kg | i.v. | 7016 ng·h/mL | 4.3 h | 142.5 mL/h/kg | / | / | / |
| Rat | 20 mg/kg | p.o. | 2946 ng·h/mL | 7.1 h | / | 160 ng/mL | 2.1 % | 1.4 h |
| Rat | 5 mg/kg | i.p. | 9631 ng·h/mL | 5.2 h | 524.9 mL/h/kg | 1966 ng/mL | / | 0.5 h |
PROTAC MNK1 degrader-1 (100 mg/kg, i.p., daily for 14 days) has acceptable drug safety, with no evident toxicity towards other major organs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female NSG mice (5 weeks old) were injected subcutaneously into the right flank with MV4-11 cells (5 × 106 cells/mouse) to induce tumors[1].
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Dosage:20 mg/kg
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Administration:i.p., daily for 16 days and then measured body and tumor weight1.
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Result:Almost completely inhibited tumor growth with inhibition rate of over 90%.
Significantly reduced the protein level of MNK1 and p-eIF4E, but no significant change in MNK2 in tumor tissues.
Did not cause any hepatotoxicity with no distinct change in the levels of ALT, TBIL, ALP, and TBA, but significantly reduced the levels of AST, UA, BUN, and CR, protecting liver and kidney function at the therapeutic dose.
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Animal Model:Male ICR mice (6 weeks old)[1].
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Dosage:100 mg/kg
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Administration:i.p., daily for 14 days and then collected blood samples and other organs1.
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Result:Did not induce significant histopathological abnormalities in major organs (heart, liver, spleen, lungs, and kidneys), and serum biochemical parameters (ALT, DBIL, TBIL, ALP, TBA, BUN, CR, UA, and CK-MB) remained within normal physiological ranges.
Chemical Information
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CAS No. 3120743-91-8
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Appearance Solid
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Molecular Weight 670.78
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Formula C35H38N6O6S
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Color White to off-white
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SMILES
O=C(NC1=CC=CC2=C1CN(C3C(NC(CC3)=O)=O)C2=O)CCCCCC(N4CCC(C(NC5=NC=C(C6=CC=CC=C6)S5)=O)CC4)=O
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Synonyms
P11-2
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
DMSO : 100 mg/mL (149.08 mM; Need ultrasonic; 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
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Data Sheet (276 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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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 | 1.4908 mL | 7.4540 mL | 14.9080 mL | 37.2700 mL |
| 5 mM | 0.2982 mL | 1.4908 mL | 2.9816 mL | 7.4540 mL | |
| 10 mM | 0.1491 mL | 0.7454 mL | 1.4908 mL | 3.7270 mL | |
| 15 mM | 0.0994 mL | 0.4969 mL | 0.9939 mL | 2.4847 mL | |
| 20 mM | 0.0745 mL | 0.3727 mL | 0.7454 mL | 1.8635 mL | |
| 25 mM | 0.0596 mL | 0.2982 mL | 0.5963 mL | 1.4908 mL | |
| 30 mM | 0.0497 mL | 0.2485 mL | 0.4969 mL | 1.2423 mL | |
| 40 mM | 0.0373 mL | 0.1864 mL | 0.3727 mL | 0.9318 mL | |
| 50 mM | 0.0298 mL | 0.1491 mL | 0.2982 mL | 0.7454 mL | |
| 60 mM | 0.0248 mL | 0.1242 mL | 0.2485 mL | 0.6212 mL | |
| 80 mM | 0.0186 mL | 0.0932 mL | 0.1864 mL | 0.4659 mL | |
| 100 mM | 0.0149 mL | 0.0745 mL | 0.1491 mL | 0.3727 mL |
PROTAC MNK1 degrader-1 Related Classifications
HY-176428 Related Classifications
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