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  2. MAPK/ERK Pathway Autophagy
  3. Mixed Lineage Kinase Autophagy
  4. URMC-099

URMC-099 是一種口服生物有效的混合譜系激酶 3 (MLK3) (IC50=14 nM) 抑制劑，具有優(yōu)異的血腦屏障穿透性。

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URMC-099 Chemical Structure

URMC-099 Chemical Structure

CAS No. : 1229582-33-5

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2.  同一機構（單位）同一產(chǎn)品試用裝僅限申領一次，同一機構（單位）一年內

     可免費申領三個不同產(chǎn)品的試用裝。

3.  試用裝只面向終端客戶。

規(guī)格 價格 是否有貨 數(shù)量
10 mM * 1 mL in DMSO ￥1089
In-stock
1 mg ￥450
In-stock
5 mg ￥990
In-stock
10 mg ￥1500
In-stock
50 mg ￥4000
In-stock
100 mg 現(xiàn)貨 詢價
200 mg   詢價  
500 mg   詢價  

* Please select Quantity before adding items.

Customer Review

  • 生物活性

  • 實驗參考方法

  • 純度 & 產(chǎn)品資料

  • 參考文獻

生物活性

URMC-099 is an orally bioavailable and potent mixed lineage kinase type 3 (MLK3) (IC50=14 nM) inhibitor with with excellent blood-brain barrier penetration properties.

IC50 & Target

LRRK2

11 nM (IC50)

FLT3

4 nM (IC50)

FLT1

39 nM (IC50)

ABL1 (T315I)

3 nM (IC50)

ABL1

6.8 nM (IC50)

SGK

67 nM (IC50)

SGK1

201 nM (IC50)

AurA

108 nM (IC50)

AurB

123 nM (IC50)

AurC

290 nM (IC50)

IKKβ

257 nM (IC50)

IKKα

591 nM (IC50)

TNFα

460 nM (IC50)

ROCK1

1030 nM (IC50)

ROCK2

111 nM (IC50)

CDK1

1125 nM (IC50)

CDK2

1180 nM (IC50)

TRKA

85 nM (IC50)

c-MET

177 nM (IC50)

TRKB

217 nM (IC50)

IGF1R

307 nM (IC50)

LCK

333 nM (IC50)

MEKK2

661 nM (IC50)

SYK

731 nM (IC50)

AMPK

1512 nM (IC50)

JNK1

3280 nM (IC50)

SRC

4330 nM (IC50)

ZAP70

5050 nM (IC50)

ERK2

6290 nM (IC50)

P38α

12050 nM (IC50)

CYP3A4

16.2 μM (IC50)

體外研究
(In Vitro)

The effect of URMC-099 (URMC099) on the in vitro growth of the “brain homing” MDA-MB-231 BR cells expressing eGFP (eGFP8.4) and their parental cell line, MDA-MB-231 is tested. The cells are treated with either 200 nM URMC-099 or vehicle alone. Cells treated with URMC-099 grow at a similar rate to those treated with vehicle. Cell viability is >99% in all cases[2].

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

URMC-099 has moderate terminal elimination half-life (t1/2=1.92 h, 2.14 h and 2.72 h for C57 BL/6 mice (10 mg/kg, oral dosing), C57 BL/6 mice (2.5 mg/kg, iv), C57 BL/6 mice (10 mg/kg, iv))[1]. The effect of URMC-099 (URMC099) on tumor formation in vivo is analyzed using a well characterized mouse xenograft model of breast cancer brain metastasis. For these experiments, eGFP8.4 cells are inoculated into the left ventricle of immunodeficient nu/nu mice; animals are then treated with either URMC-099 (10 mg/kg) or vehicle alone, every 12 hours for 20 days. This dose of URMC-099 is chosen because it has been shown to be sufficient to effectively inhibit MLK3 in mice, with good penetration of the blood-brain barrier and potent inhibition of the phosphorylation of Jun N-terminal kinase (JNK) in brain tissue. On day 21 the mice are sacrificed and number of BM is assessed. Fifteen mice are used for each treatment group. BM are detected in 60% of mice, which is consistent with previous studies using this xenograft model by other investigators. URMC-099 treatment significantly (p<0.05, two-tailed t-test) increases the total number of brain metastasis (BM) in mice. For micrometastases, the pattern is similar to that observed for total BM. The number of macrometastases is statistically indistinguishable between mice treated with URMC-099 or vehicle[2].

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

421.54

Formula

C27H27N5
CAS 號
性狀

固體

顏色

Off-white 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(shù)據(jù)
細胞實驗： 

DMSO 中的溶解度 : ≥ 33 mg/mL (78.28 mM; 吸濕的 DMSO 對產(chǎn)品的溶解度有顯著影響，請使用新開封的 DMSO)

* "≥" means soluble, but saturation unknown.

配制儲備液
濃度 溶劑體積 質量 1 mg 5 mg 10 mg
1 mM 2.3723 mL 11.8613 mL 23.7225 mL
5 mM 0.4745 mL 2.3723 mL 4.7445 mL
查看完整儲備液配制表

* 請根據(jù)產(chǎn)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(chǎn)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

動物實驗：

請根據(jù)您的 實驗動物和給藥方式 選擇適當?shù)娜芙夥桨浮?

以下溶解方案都請先按照 In Vitro 方式配制澄清的儲備液，再依次添加助溶劑：
——為保證實驗結果的可靠性，澄清的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的工作液，建議您現(xiàn)用現(xiàn)配，當天使用；
以下溶劑前顯示的百分比是指該溶劑在您配制終溶液中的體積占比；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的方式助溶

  • 方案 一

    請依序添加每種溶劑： 5% DMSO    40% PEG300    5% Tween-80    50% Saline

    Solubility: ≥ 2.87 mg/mL (6.81 mM); 澄清溶液

  • 方案 二

    請依序添加每種溶劑： 5% DMSO    95% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2.87 mg/mL (6.81 mM); 澄清溶液

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(shù)量

只
由于實驗過程有損耗，建議您多配一只動物的量
請輸入您的動物體內配方組成：
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
如果您的動物是免疫缺陷鼠或者體弱鼠，建議 DMSO 中的在最后工作液體系中的占比盡量不超過 2%。
方案所需 助溶劑 包括：DMSO， ，均可在 MCE 網(wǎng)站選購。 ，Tween 80，均可在 MCE 網(wǎng)站選購。
計算結果
工作液所需濃度 : mg/mL
儲備液配制方法 : mg 藥物溶于 μL  DMSO（母液濃度為 mg/mL）。
您所需的儲備液濃度超過該產(chǎn)品的實測溶解度，以下方案僅供參考，如有需要，請與 MCE 中國技術支持聯(lián)系。
動物實驗體內工作液的配制方法 : 取 μL DMSO 儲備液，加入 μL 。 μL ，混合均勻至澄清，再加 μL Tween 80，混合均勻至澄清，再加 μL 生理鹽水。
連續(xù)給藥周期超過半月以上，請謹慎選擇該方案。
請確保第一步儲備液溶解至澄清狀態(tài)，從左到右依次添加助溶劑。您可采用超聲加熱 （超聲清洗儀，建議頻次 20-40 kHz），渦旋吹打等方式輔助溶解。
純度 & 產(chǎn)品資料

純度: 99.34%

參考文獻
Cell Assay
[2]

MDA-MB-231, MCF10A, HS578t and MDA-MB-231 EGFP8.4 cells are seeded in a 24 well plate at an initial density of 5.0×104 cells/mL in 0.5 mL of media. The cells are treated with either 200 μM of URMC-099 or vehicle (0.002% DMSO). Cell number in each well is measured by trypsinizing the cells and counting them with a hematocytometer. The viability is tested by trypan blue dye exclusion. Each condition is tested in triplicate[2].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[2]

Mice[2]
6 to 8 week old female nu/nu mice are injected intraperitoneally with URMC-099 at a dose of 10 mg/kg, or vehicle, twice daily for 20 days. On day 21 mice are sacrificed by CO2 suffocation. Brains are removed and fixed with 4% formaldehyde in PBS overnight, then transferred to 30% sucrose in PBS. The brains are then quickly frozen by immersing into isopentane cooled on dry ice. The frozen brains are sectioned coronally every 30 micrometers. Eight sections starting at bregma 2.0 and separated by 360 μm are mounted on glass slides for tumor evaluation under the microscope. The number of brain metastasis (BM) is counted by examining eGFP signals under a fluorescence microscope at 20× magnification[2].

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(jù)產(chǎn)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(chǎn)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 2.3723 mL 11.8613 mL 23.7225 mL 59.3064 mL
5 mM 0.4745 mL 2.3723 mL 4.7445 mL 11.8613 mL
10 mM 0.2372 mL 1.1861 mL 2.3723 mL 5.9306 mL
15 mM 0.1582 mL 0.7908 mL 1.5815 mL 3.9538 mL
20 mM 0.1186 mL 0.5931 mL 1.1861 mL 2.9653 mL
25 mM 0.0949 mL 0.4745 mL 0.9489 mL 2.3723 mL
30 mM 0.0791 mL 0.3954 mL 0.7908 mL 1.9769 mL
40 mM 0.0593 mL 0.2965 mL 0.5931 mL 1.4827 mL
50 mM 0.0474 mL 0.2372 mL 0.4745 mL 1.1861 mL
60 mM 0.0395 mL 0.1977 mL 0.3954 mL 0.9884 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(chǎn)品名稱：
URMC-099
目錄號：
HY-12599
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