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  1. Protein Tyrosine Kinase/RTK Apoptosis Cell Cycle/DNA Damage Epigenetics Stem Cell/Wnt JAK/STAT Signaling PI3K/Akt/mTOR MAPK/ERK Pathway
  2. Anaplastic lymphoma kinase (ALK) Apoptosis ROS Kinase Caspase PARP IGF-1R STAT Akt JNK
  3. ASP3026

ASP3026 是一種具有選擇性和口服活性的間變性淋巴瘤激酶 (ALK) 抑制劑,IC50 值是 3.5 nM。ASP3026 可抑制 IGF-1R,STAT3,AKTJNK 蛋白的磷酸化,和誘導(dǎo)caspase 3PARP裂解,同時(shí)對(duì) ROSACK 也有抑制作用。ASP3026 可用于抗癌研究。

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ASP3026 Chemical Structure

ASP3026 Chemical Structure

CAS No. : 1097917-15-1

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10 mM * 1 mL in DMSO ¥1780
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Customer Review

  • 生物活性

  • 純度 & 產(chǎn)品資料

  • 參考文獻(xiàn)

生物活性

ASP3026 is a selective and orally active inhibitor of anaplastic lymphoma kinase (ALK). ASP3026 is a selective and oral active anaplastic lymphoma kinase (ALK) inhibitor with a IC50 value of 3.5 nM. ASP3026 can inhibit the phosphorylation of IGF-1R, STAT3, AKT and JNK proteins, and induce the cleavage of caspase 3 and PARP. It also inhibited ROS and ACK. ASP3026 can be used in anti-tumor research[1][2][3][4].

IC50 & Target

ROS

 

ACK

 

Caspase-3

 

PARP1

 

IGF-1R

 

STAT3

 

細(xì)胞效力
(Cellular Effect)
Cell Line Type Value Description References
BaF3 IC50
1508 nM
Compound: 20; ASP3026
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/T790M/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
[PMID: 33243531]
BaF3 IC50
17 nM
Compound: 2; ASP3026
Inhibition of EML4-fused ALK variant 1 (unknown origin) expressed in mouse BAF3 cells using peptide substrate measured after 1 hr by HTRF assay
Inhibition of EML4-fused ALK variant 1 (unknown origin) expressed in mouse BAF3 cells using peptide substrate measured after 1 hr by HTRF assay
[PMID: 30878193]
BaF3 IC50
323.9 nM
Compound: 20; ASP3026
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
Cytotoxicity against mouse BaF3 cells expressing human EGFR C797S/del19 mutant assessed as inhibition of in cell viability measured after 72 hrs by CellTiter-Glo assay
[PMID: 33243531]
體外研究
(In Vitro)

ASP3026 (0.1-2.5 μM, 24-72 h) 降低 NPM-ALK+ ALCL 細(xì)胞的活力、增殖和集落形成,并誘導(dǎo)細(xì)胞凋亡[2]。
ASP3026 (0.1-2.5 μM, 24-72 h) 顯著降低轉(zhuǎn)染對(duì) Crizotinib (HY-50878) 耐藥的 NPM-ALK 突變體的 293T 細(xì)胞的增殖,并下調(diào)這些突變體的酪氨酸磷酸化[2]。
ASP3026 (1-4 μg/ml, 48 h) 可以抑制紅細(xì)胞在能量耗盡和氧化應(yīng)激后的細(xì)胞膜崩潰,并由此抵消自殺性紅細(xì)胞死亡和隨后貧血的發(fā)展[3]。
ASP3026 (100 nM, 1000 nM, 5 days) 以 ATP 競(jìng)爭(zhēng)性方式抑制 ALK 活性,其抑制譜與 ALK/MET 雙重抑制劑 Crizotinib (HY-50878) 不同[4]。

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

Western Blot Analysis[2]

Cell Line: NPM-ALK+ ALCL cell, 50-80 μg total proteins
Concentration: 0.1-2.5 μM
Incubation Time: 24-72 h
Result: Significantly decreased the activity of NPM-ALK tyrosine kinase and the tyrosine phosphorylation levels at Y646 and Y664, and decreased the phosphorylation levels of IGF-IR, STAT3, AKT and JNK proteins, the target proteins of NPM-ALK signal transduction.
Successfully induced the cleavage of caspase 3 and PARP, which further indicated that it induced the apoptosis of NPM-ALK+ ALCL cells.

Cell Viability Assay[2]

Cell Line: NPM-ALK+ T-cell ALCL cell lines Karpas 299, SU-DHL-1, SUP-M2, SR-786, DEL
Concentration: 0.1-2.5 μM
Incubation Time: 24-72 h
Result: At 48 h, the IC50 values of SU-DHL-1, SUP-M2, SR-786, Karpas 299 and DEL were 0.4 μM, 0.75 μM, 1.0 μM, 2.5 μM and greater than 3.0 μM, respectively.
Significantly reduced the viability of lymphoma cells than that of T lymphocytes.
At 72 h, the IC50 values of SU-DHL-1, SUP-M2, SR-786, Karpas 299 and DEL were 0.3 μM, 0.75 μM, 0.75 μM, 2.5 μM and 0.5 μM, respectively.

Cell Proliferation Assay[4]

Cell Line: NCI-H2228 NSCLC
Concentration: 100 nM, 1000 nM
Incubation Time: 5 days
Result: Inhibited the growth of ALK-dependent cells.
Inhibited the growth of NCI-H2228 cells with an IC50 value of 64.8 nM.
體內(nèi)研究
(In Vivo)

ASP3026 (30 mg/kg daily for 10 weeks, p.o.) 抑制小鼠體內(nèi) NPM-ALK+ ALCL 腫瘤細(xì)胞生長(zhǎng)[2]。
ASP3026 (10 mg/kg daily for 5 days, p.o.) 可增強(qiáng)紫杉醇 Paclitaxel (HY-B0015) 和培美曲塞 Pemetrexed (HY-10820) 的抗腫瘤活性,單獨(dú)使用時(shí)可誘導(dǎo)非小細(xì)胞肺癌模型小鼠腫瘤消退并延長(zhǎng)生存期,且不影響非小細(xì)胞肺癌模型小鼠的體重[4]

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

Animal Model: Female C.B-17 SCID mice of systemic xenograft lymphoma model[2]
Dosage: 30 mg/kg daily for 10 weeks
Administration: p.o.
Result: Mice in the ASP3026-interrupted group developed recurrent lymphoma, were subsequently treated with ASP3026 and survived until the end of the study.
Clinical Trial
分子量

580.74

Formula

C29H40N8O3S

CAS 號(hào)
性狀

固體

顏色

White to off-white

運(yùn)輸條件

Room temperature in continental US; may vary elsewhere.

儲(chǔ)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(xì)胞實(shí)驗(yàn): 

DMSO 中的溶解度 : 20 mg/mL (34.44 mM; 超聲助溶; 吸濕的 DMSO 對(duì)產(chǎn)品的溶解度有顯著影響,請(qǐng)使用新開(kāi)封的 DMSO)

配制儲(chǔ)備液
濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg
1 mM 1.7219 mL 8.6097 mL 17.2194 mL
5 mM 0.3444 mL 1.7219 mL 3.4439 mL
查看完整儲(chǔ)備液配制表

* 請(qǐng)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(chǔ)備液;一旦配成溶液,請(qǐng)分裝保存,避免反復(fù)凍融造成的產(chǎn)品失效
儲(chǔ)備液的保存方式和期限:-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí),請(qǐng)?jiān)?年內(nèi)使用, -20°C儲(chǔ)存時(shí),請(qǐng)?jiān)?年內(nèi)使用。

  • 摩爾計(jì)算器

  • 稀釋計(jì)算器

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

質(zhì)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(dòng)物實(shí)驗(yàn):

請(qǐng)根據(jù)您的 實(shí)驗(yàn)動(dòng)物和給藥方式 選擇適當(dāng)?shù)娜芙夥桨浮?

以下溶解方案都請(qǐng)先按照 In Vitro 方式配制澄清的儲(chǔ)備液,再依次添加助溶劑:
——為保證實(shí)驗(yàn)結(jié)果的可靠性,澄清的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件,適當(dāng)保存;體內(nèi)實(shí)驗(yàn)的工作液,建議您現(xiàn)用現(xiàn)配,當(dāng)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(guò)程中出現(xiàn)沉淀、析出現(xiàn)象,可以通過(guò)加熱和/或超聲的方式助溶

  • 方案 一

    請(qǐng)依序添加每種溶劑: 10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 2 mg/mL (3.44 mM); 澄清溶液

    此方案可獲得 ≥ 2 mg/mL(飽和度未知)的澄清溶液。

    1 mL 工作液為例,取 100 μL 20.0 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 400 μL PEG300 中,混合均勻;再向上述體系中加入 50 μL Tween-80,混合均勻;然后再繼續(xù)加入 450 μL 生理鹽水 定容至 1 mL

    生理鹽水的配制:將 0.9 g 氯化鈉,溶解于 ddH?O 并定容至 100 mL,可以得到澄清透明的生理鹽水溶液。
  • 方案 二

    請(qǐng)依序添加每種溶劑: 10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 2 mg/mL (3.44 mM); 澄清溶液

    此方案可獲得 ≥ 2 mg/mL(飽和度未知)的澄清溶液。

    1 mL 工作液為例,取 100 μL 20.0 mg/mL 的澄清 DMSO 儲(chǔ)備液加到 900 μL 20% 的 SBE-β-CD 生理鹽水水溶液 中,混合均勻。

    2 g SBE-β-CD(磺丁基醚 β-環(huán)糊精)粉末定容于 10 mL 的生理鹽水中,完全溶解至澄清透明。
動(dòng)物溶解方案計(jì)算器
請(qǐng)輸入動(dòng)物實(shí)驗(yàn)的基本信息:

給藥劑量

mg/kg

動(dòng)物的平均體重

g

每只動(dòng)物的給藥體積

μL

動(dòng)物數(shù)量

由于實(shí)驗(yàn)過(guò)程有損耗,建議您多配一只動(dòng)物的量
請(qǐng)輸入您的動(dòng)物體內(nèi)配方組成:
%
DMSO +
+
%
Tween-80 +
%
Saline
如果您的動(dòng)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(guò) 2%。
方案所需 助溶劑 包括:DMSO ,均可在 MCE 網(wǎng)站選購(gòu)。 ,Tween 80,均可在 MCE 網(wǎng)站選購(gòu)。
計(jì)算結(jié)果
工作液所需濃度 : mg/mL
儲(chǔ)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(chǔ)備液濃度超過(guò)該產(chǎn)品的實(shí)測(cè)溶解度,以下方案僅供參考,如有需要,請(qǐng)與 MCE 中國(guó)技術(shù)支持聯(lián)系。
動(dòng)物實(shí)驗(yàn)體內(nèi)工作液的配制方法 : 取 μL DMSO 儲(chǔ)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(guò)半月以上,請(qǐng)謹(jǐn)慎選擇該方案。
請(qǐng)確保第一步儲(chǔ)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: 99.88%

參考文獻(xiàn)

完整儲(chǔ)備液配制表

* 請(qǐng)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(chǔ)備液;一旦配成溶液,請(qǐng)分裝保存,避免反復(fù)凍融造成的產(chǎn)品失效
儲(chǔ)備液的保存方式和期限:-80°C, 2 years; -20°C, 1 year。-80°C儲(chǔ)存時(shí),請(qǐng)?jiān)?年內(nèi)使用, -20°C儲(chǔ)存時(shí),請(qǐng)?jiān)?年內(nèi)使用。

可選溶劑 濃度 溶劑體積 質(zhì)量 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 1.7219 mL 8.6097 mL 17.2194 mL 43.0485 mL
5 mM 0.3444 mL 1.7219 mL 3.4439 mL 8.6097 mL
10 mM 0.1722 mL 0.8610 mL 1.7219 mL 4.3049 mL
15 mM 0.1148 mL 0.5740 mL 1.1480 mL 2.8699 mL
20 mM 0.0861 mL 0.4305 mL 0.8610 mL 2.1524 mL
25 mM 0.0689 mL 0.3444 mL 0.6888 mL 1.7219 mL
30 mM 0.0574 mL 0.2870 mL 0.5740 mL 1.4350 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:
ASP3026
目錄號(hào):
HY-13326
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