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

ROTAC MNK1 degrader-1 是一种选择性 MNK1 PROTAC 降解剂，其在 MV4-11 细胞中的 DC50 为 11.92 nM，Dmax > 96%。PROTAC MNK1 degrader-1 显著降低 p-eIF4E 水平 (IC50 为 22.07 nM)，诱导细胞凋亡 (apoptosis)，并将细胞周期阻滞于 G1 期。PROTAC MNK1 degrader-1 具有强效的抗肿瘤活性。PROTAC MNK1 degrader-1 在 MV4-11 异种移植小鼠模型中表现出强大的抗白血病功效，且具有可接受的药物安全性。粉色：MNK1 ligand (HY-176429)；蓝色：CRBN ligase ligand (HY-A0003)；黑色：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 相关抗体

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MNK1 MNK2 MNK

  • 生物活性

  • 纯度 & 产品资料

  • 参考文献

生物活性

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)

体外研究
(In Vitro)

PROTAC MNK1 degrader-1 (Compound P11-2) (0.001-10 μM，24 小时) 显著增强了四种癌细胞系的抗增殖活性，对 MV4-11、MM.1S、MOLM-13 和 MDA-MB-231 细胞的 IC50 分别为 0.045、0.24、0.61 和 2.06 μM[1]。
PROTAC MNK1 degrader-1 (300 nM，1-24 小时) 以 CRBN 和蛋白酶体依赖性方式诱导在 MV4-11 细胞中 的 MNK1 降解，其 t1/2 为 3.64 小时[1]。
PROTAC MNK1 degrader-1 (10-1000 nM，24小时) 通过选择性降解 MV4-11 细胞中 MNK1 并降低下游因子 p-eIF4E 的蛋白水平，IC50 为 22.07 nM，进而有效抑制的肿瘤细胞增殖[1]。
PROTAC MNK1 degrader-1 对 CRBN 和 MNK1 的活性位点具有优异的结合能力，其连接子与 H353 形成氢键[1]。
PROTAC MNK1 degrader-1 (30-300 nM，24小时) 以剂量依赖性方式诱导 MV4-11 细胞凋亡 (尤其是晚期凋亡)，并将细胞周期停滞在 G1 期[1]。

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

PROTAC MNK1 degrader-1 相关抗体:

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.
药代动力学
(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
体内研究
(In Vivo)

PROTAC MNK1 degrader-1 (Compound P11-2) (20 mg/kg，腹腔注射，每日一次，共 16 天) 通过降解 MV4-11 异种移植小鼠模型中的 MNK1 显著抑制肿瘤生长，并进一步降低 p-eIF4E 水平[1]。
PROTAC MNK1 degrader-1 (100 mg/kg，腹腔注射，每日一次，共 14 天) 具有可接受的药物安全性，对其他主要器官无明显毒性[1]。

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.
分子量

670.78

Formula

C35H38N6O6S
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
纯度 & 产品资料
参考文献

PROTAC MNK1 degrader-1 相关分类

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  • 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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