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  2. MAPK/ERK Pathway
  3. Mixed Lineage Kinase
  4. M443

M443 是 MRK 的一個不可逆的、特異性抑制劑，其 IC50 值 <125 nM。

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M443 Chemical Structure

M443 Chemical Structure

CAS No. : 1820684-31-8

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規(guī)格 價格 是否有貨 數量
10 mM * 1 mL in DMSO ￥5189
In-stock
1 mg ￥1600
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5 mg ￥4000
In-stock
10 mg 現貨 詢價
50 mg   詢價  
100 mg   詢價  

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Customer Review

MCE 顧客使用本產品發(fā)表的 3 篇科研文獻

  • 生物活性

  • 實驗參考方法

  • 純度 & 產品資料

  • 參考文獻

生物活性

M443 is an irreversible and specific inhibitor of MRK, with an IC50<125 nM.

IC50 & Target

IC50: <125 nM (MRK)[1].
體外研究
(In Vitro)

MRK depletion decreases cell viability after IR by 33% of control at 3 Gy. Similarly, the clonogenic assay shows a significant decrease in survival with a dose enhancement factor (DEF) of 1.6 at 10% viability. MRK activation by IR is maximal at 30 minutes after exposure to radiation. Therefore, for subsequent analysis, this time point is used. In both cell cultures, the IR-stimulated activation of MRK, Chk2, and p38 is greatly inhibited by 500 nM M443. Cells are seeded on coverslips, pretreated with 500 nM M443 or vehicle, exposed to 6 Gy of IR, fixed at different times after IR and processed for immunofluorescence with the MPM2 phospho-specific antibody that specifically stains mitotic cells. In contrast to control cells, the M443-treated cells fail to arrest after IR and maintained a similar mitotic index as the nonirradiated cells. Thus, inhibition of MRK leads to inhibition of Chk2 and failure to arrest in the cell cycle in response to IR-induced DNA damage[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
體內研究
(In Vivo)

Control mice survive with a median of 32 days after tumor cell implantation. Treatment with M443 alone adds 5.5 days to this survival, whereas the chosen low dose of radiation does not significantly increase survival. In contrast, the combination of M443 and IR extend survival with a median of 16 days longer than control. Treatment with M443 does not affect the animal weight, as the weight loss observed is observed in all groups just a few days before the animals became moribund. It is showed that the tumor-containing fraction has elevated levels of both total and active MRK (lane RB in the vehicle-treated brain). In contrast, the tumor-containing fraction from the M443-treated brain shows total loss of MRK activity. Interestingly, the fractions containing normal brain, which in the control brain show some level of MRK protein, in the treated brain also has lost MRK, suggesting that diffusion of M443 across the whole cerebellum inhibit normal MRK as well[1].

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

589.61

Formula

C31H30F3N7O2
CAS 號
性狀

固體

顏色

Light yellow to yellow

運輸條件

Room temperature in continental US; may vary elsewhere.
儲存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 2 years
-20°C 1 year
溶解性數據
細胞實驗： 

DMSO 中的溶解度 : 55 mg/mL (93.28 mM; 超聲助溶; 吸濕的 DMSO 對產品的溶解度有顯著影響，請使用新開封的 DMSO)

配制儲備液
濃度 溶劑體積 質量 1 mg 5 mg 10 mg
1 mM 1.6960 mL 8.4802 mL 16.9604 mL
5 mM 0.3392 mL 1.6960 mL 3.3921 mL
查看完整儲備液配制表

* 請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內使用， -20°C儲存時，請在1年內使用。

  • 摩爾計算器

  • 稀釋計算器

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

質量
=
濃度
×
體積
×
分子量 *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

濃度 (start)

C1

×
體積 (start)

V1

=
濃度 (final)

C2

×
體積 (final)

V2

動物溶解方案計算器
請輸入動物實驗的基本信息：

給藥劑量

mg/kg

動物的平均體重

g

每只動物的給藥體積

μL

動物數量

只
由于實驗過程有損耗，建議您多配一只動物的量
計算結果
工作液所需濃度 : mg/mL
純度 & 產品資料

純度: 98.95%

參考文獻
Cell Assay
[1]

Two days after transfection with siRNAs, medulloblastoma cells are seeded in a 96-well plate, and the following day, they are exposed to different doses of radiation. Cell viability is determined 72 hours after radiation treatment by MTT absorbance at 595 nm. For cells that are treated with M443 (250 nM, 500 nM), 6 hours after treatment with different concentrations of the drug or vehicle control, they are exposed to radiation and processed for the MTT assay 72 hours later as above. Five hundred cells are seeded in 6 cm dishes 2 days after siRNA transfections. The following day, cells are exposed to the different doses of radiation using a biologic irradiator and cultured for 7 days with media changes every other day. Colonies containing more than 50 cells are counted, and the results are used to calculate the surviving fractions. For the treatment with M443 or vehicle control, 24 hours after seeding, cells are exposed to the drug for 6 hours and subsequently to radiation[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[1]

Mice[1]
The primary UI226 medulloblastoma cells are patient derived xenografts. UI226 is largely propagated as flank cultures in nude mice and cultured in StemPro media for less than 3 weeks before intracranial injections. Medulloblastoma cells (5.0×105 UI226 in 5 mL of StemPro medium) are injected over 5 minutes into the cerebellum of 4-week-old athymic female mice. Three weeks after tumor cell implantation and approximately 2 weeks before the animals become moribund; treatment is started by implantation of an osmotic pump filled with either 0.05 mg/mL solution of M443 or vehicle (0.01% DMSO in PBS) and implanted in a subcutaneous pocket on the dorsal flank of the animal. A catheter with attached cannula delivers the drug intracranially and directly into the tumor over a period of 2 weeks, at a steady rate of 0.25 mL/hour. Irradiation of the mice head is initiated 2 days after pump implantation and conducted over 2 days[1].

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

完整儲備液配制表

* 請根據產品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；一旦配成溶液，請分裝保存，避免反復凍融造成的產品失效。
儲備液的保存方式和期限：-80°C, 2 years; -20°C, 1 year。-80°C儲存時，請在2年內使用， -20°C儲存時，請在1年內使用。

可選溶劑 濃度 溶劑體積 質量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.6960 mL 8.4802 mL 16.9604 mL 42.4009 mL
5 mM 0.3392 mL 1.6960 mL 3.3921 mL 8.4802 mL
10 mM 0.1696 mL 0.8480 mL 1.6960 mL 4.2401 mL
15 mM 0.1131 mL 0.5653 mL 1.1307 mL 2.8267 mL
20 mM 0.0848 mL 0.4240 mL 0.8480 mL 2.1200 mL
25 mM 0.0678 mL 0.3392 mL 0.6784 mL 1.6960 mL
30 mM 0.0565 mL 0.2827 mL 0.5653 mL 1.4134 mL
40 mM 0.0424 mL 0.2120 mL 0.4240 mL 1.0600 mL
50 mM 0.0339 mL 0.1696 mL 0.3392 mL 0.8480 mL
60 mM 0.0283 mL 0.1413 mL 0.2827 mL 0.7067 mL
80 mM 0.0212 mL 0.1060 mL 0.2120 mL 0.5300 mL
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.

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產品名稱：
M443
目錄號：
HY-112274
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