2. PROTAC MAPK/ERK Pathway Apoptosis Cell Cycle/DNA Damage
  3. PROTACs MNK Apoptosis Eukaryotic Initiation Factor (eIF)
  4. PROTAC MNK1 degrader-1

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: CRBN ligase ligand (HY-A0003); Black: linker (HY-Y1139); CRBN + linker: HY-176430

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PROTAC MNK1 degrader-1 Chemical Structure

PROTAC MNK1 degrader-1 Chemical Structure

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PROTAC MNK1 degrader-1 Related Antibodies

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Description

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[1]. Pink: MNK1 ligand (HY-176429); Blue: CRBN ligase ligand (HY-A0003); Black: linker (HY-Y1139); CRBN + linker: HY-176430

IC50 & Target

MNK1

11.92 nM (DC50)

eIF4

22.07 nM (IC50)

In Vitro

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.

PROTAC MNK1 degrader-1 Related Antibodies

Western Blot Analysis[1]

Cell Line: MV4-11 cells
Concentration: 0.001, 0.003, 0.01, 0.03, 0.1, 0.3, 1, 3 μM
Incubation Time: 1, 2, 4, 8, 16, 24 h
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.

Western Blot Analysis[1]

Cell Line: MOLM-13, MM.1S, MDA-MB-231 cells
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)
Incubation Time: 24 h
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.

Apoptosis Analysis[1]

Cell Line: MV4-11 cells
Concentration: 30, 100, 300 nM
Incubation Time: 24 h
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.

Cell Cycle Analysis[1]

Cell Line: MV4-11 cells
Concentration: 30, 100, 300 nM
Incubation Time: 24 h
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.
Parmacokinetics
Species Dose SampleTime Route Indicator value
Rat 1 mg/kg 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 h i.v. AUC0-t 7016 ng·h/mL
Rat 20 mg/kg 0.25, 0.5, 1, 2, 4, 8, 12, 24 p.o. AUC0-t 2946 ng·h/mL
Rat 5 mg/kg i.p. AUC0-t 9631 ng·h/mL
Rat 1 mg/kg 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 h i.v. CL 142.5 mL/h/kg
Rat 1 mg/kg 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, 24 h i.v. T1/2 4.3 hr
Rat 20 mg/kg 0.25, 0.5, 1, 2, 4, 8, 12, 24 p.o. Cmax 160 ng/mL
Rat 5 mg/kg i.p. Cmax 1966 ng/mL
Rat 20 mg/kg 0.25, 0.5, 1, 2, 4, 8, 12, 24 p.o. F 2.1 %
Rat 5 mg/kg i.p. CL 524.9 mL/h/kg
Rat 20 mg/kg 0.25, 0.5, 1, 2, 4, 8, 12, 24 p.o. T1/2 7.1 hr
Rat 5 mg/kg i.p. T1/2 5.2 hr
Rat 20 mg/kg 0.25, 0.5, 1, 2, 4, 8, 12, 24 p.o. Tmax 1.4 hr
Rat 5 mg/kg i.p. Tmax 0.5 hr
In Vivo

PROTAC MNK1 degrader-1 (Compound P11-2) (20 mg/kg, i.p., daily for 16 days) significantly inhibits tumor growth by the degradation of MNK1 and further reducing the level of p-eIF4E in the MV4-11 xenograft mice model[1].
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.

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].
Dosage: 20 mg/kg
Administration: i.p., daily for 16 days and then measured body and tumor weight1.
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.
Animal Model: Male ICR mice (6 weeks old)[1].
Dosage: 100 mg/kg
Administration: i.p., daily for 14 days and then collected blood samples and other organs1.
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.
Molecular Weight

670.78

Formula

C35H38N6O6S
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
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
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PROTAC MNK1 degrader-1 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PROTAC MNK1 degrader-1PROTACsMNKApoptosisEukaryotic Initiation Factor (eIF)Mitogen activated protein kinase interacting kinaseMAP kinase interacting kinaseMAPK interacting kinasePROTACDegradationAnticancerMV4-11 xenograft modelMV4-11 cellsMM.1S cellsMOLM-13 cellsMDA-MB-231 cellsInhibitorinhibitorinhibit

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