Torkinib (PP242)
Torkinib (PP242) 是一种选择性的mTOR抑制剂，在无细胞试验中IC50为8 nM；靶向作用于mTOR复合体，作用于mTOR比作用于PI3Kδ或PI3Kα/β/γ选择性分别高10倍多和100倍。Torkinib (PP242) 可诱导线粒体自噬和凋亡。
Torkinib (PP242) Chemical Structure
CAS: 1092351-67-1
产品质控
批次：
纯度：
99.50%
99.50
Torkinib (PP242)相关产品
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| HT-p21 | Function Assay | 50-1250 nM | 24 h | inhibits phosphorylation of S6 kinase (target of mTORC1) and its downstream target phospho-S6 | 26177051 |
| U87vIII | Function Assay | 0.04-2.5 μM | 24 h | inhibits mTORC1 and mTORC2 activities | 26134617 |
| U87vIII | Function Assay | 2.5/5 μM | 12 h | inhibits gap closing in a dose-dependent manner | 26134617 |
| 3T3-L1 | Function Assay | 15 μM | 4 h | suppresses expression of the Egr1 protein | 25814662 |
| Rh30 | Function Assay | 1 μM | 2 h | inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt | 25762619 |
| HT29 | Function Assay | 1 μM | 2 h | inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt | 25762619 |
| Rh30 | Function Assay | 1 μM | 2 h | suppresses the basal or IGF-1-stimulated cell adhesion | 25762619 |
| HT29 | Function Assay | 1 μM | 2 h | suppresses the basal or IGF-1-stimulated cell adhesion | 25762619 |
| U87 | Growth Inhibition Assay | 25 nM | 24 h | increases DUSP10 knocked-down induced cell inhibition | 25568665 |
| AGS | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| MKN45 | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| MKN28 | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| KATO3 | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| SGC7901 | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| N87 | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| HMEC | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| HUVEC | Cell Viability Assay | 0-1000 nM | 24/48 h | decreases cell viability in time and dose dependent manner | 25035961 |
| MG63 | Function Assay | 50-1000 nM | 0.5 h | dose dependently (50–1000 nM) inhibits phosphorylation of Akt | 24840134 |
| U2OS | Function Assay | 50-1000 nM | 0.5 h | dose dependently (50–1000 nM) inhibits phosphorylation of Akt | 24840134 |
| Saos-2 | Function Assay | 50-1000 nM | 0.5 h | dose dependently (50–1000 nM) inhibits phosphorylation of Akt | 24840134 |
| Saos-2 | Function Assay | 100 nM | 0.5 h | prevents osteosarcoma cell migration | 24840134 |
| MG63 | Apoptosis Assay | 100 nM | 36 h | promotes apoptosis | 24840134 |
| U2OS | Apoptosis Assay | 100 nM | 36 h | promotes apoptosis | 24840134 |
| Saos-2 | Apoptosis Assay | 100 nM | 36 h | promotes apoptosis | 24840134 |
| DLD-1 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Caco2 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| HT29 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| H116 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Hct-8 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Colo320 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Sw948 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Colo205 | Cell Viability Assay | 0-1000 nM | 24 h | inhibits the growth in a dose-dependent manner | 23991179 |
| Colo320 | Function Assay | 1 μM | 0-24 h | abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45 | 23991179 |
| HT29 | Function Assay | 1 μM | 0-24 h | abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45 | 23991179 |
| Sw948 | Function Assay | 1 μM | 0-24 h | abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45 | 23991179 |
| DLD-1 | Function Assay | 1 μM | 0-24 h | abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45 | 23991179 |
| 786-O | Function Assay | 0.1/0.5 μM | 24 h | increases E-cadherin mRNA levels dose dependently | 23147251 |
| 786-O | Function Assay | 0-0.5 μM | 24 h | results in a dose dependent increase in E-cadherin protein expression | 23147251 |
| OCI-AML3 | Apoptosis Assay | 2.5 μM | 72 h | induces apoptosis | 22826565 |
| Jurkat | Function Assay | 100/200/400 nM | 18 h | inhibits mTORC1-dependent S6 S235/236 phosphorylation | 22566604 |
| p210 BCR-Abl | Function Assay | 100/200/400 nM | 18 h | inhibits mTORC1-dependent S6 S235/236 phosphorylation | 22566604 |
| Jurkat | Growth Inhibition Assay | 400nM | 24/48 h | synergize with 17-AAG to suppress cell proliferation | 22566604 |
| p210 BCR-Abl | Growth Inhibition Assay | 400nM | 24/48 h | synergize with 17-AAG to suppress cell proliferation | 22566604 |
| 8226 | Function Assay | 100-1000 nM | 30 min | activates ERK | 22556409 |
| MM1.S | Function Assay | 100-1000 nM | 30 min | activates ERK | 22556409 |
| 8226 | Function Assay | 0.5 μM | 30 min | induces activation of RAF and phosphorylation of MEK | 22556409 |
| MM1.S | Function Assay | 0.5 μM | 30 min | induces activation of RAF and phosphorylation of MEK | 22556409 |
| MCF-7 | Function Assay | 50/200/500 nM | 30 min | dose-dependently (50–500 nM) suppresses phosphorylation of Akt | 22476852 |
| T47D | Function Assay | 50/200/500 nM | 30 min | dose-dependently (50–500 nM) suppresses phosphorylation of Akt | 22476852 |
| MDA-MB-231 | Function Assay | 50/200/500 nM | 30 min | dose-dependently (50–500 nM) suppresses phosphorylation of Akt | 22476852 |
| Bcap-37 | Function Assay | 50/200/500 nM | 30 min | dose-dependently (50–500 nM) suppresses phosphorylation of Akt | 22476852 |
| MCF-7 | Apoptosis Assay | 200 nM | 36 h | induces apoptosis | 22476852 |
| MDA-MB-231 | Apoptosis Assay | 200 nM | 36 h | induces apoptosis | 22476852 |
| Bcap-37 | Apoptosis Assay | 200 nM | 36 h | induces apoptosis | 22476852 |
| LS174T | Function Assay | 10/100/1000 nM | 6 h | inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein | 22401294 |
| DLD-1 | Function Assay | 10/100/1000 nM | 6 h | inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein | 22401294 |
| SW480 | Function Assay | 10/100/1000 nM | 6 h | inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein | 22401294 |
| NIH 3T3 | Function Assay | 2 μM | 18 h | inhibits mTORC2 phosphorylation of Akt on Ser473 and mTORC1 phosphorylation of 4E-BP1 on Thr37/46 | 21876130 |
| HCT15 | Function Assay | 0.5/2 μM | 4 h | prevents S6K1 phosphorylation of ribosomal protein S6 at Ser240/244 and mTORC2 phosphorylation of Akt at Ser473 | 21876130 |
| SW620 | Function Assay | 0.5/2 μM | 4 h | blocks all three mTOR outputs | 21876130 |
| PC12 | Function Assay | 40 nM | induces lysosomal biogenesis and alleviated α-SYN accumulation | 26001614 | |
| DND-1 | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| TMD8 | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| Jurkat | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| KOPT-K1 | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| TMD7 | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| THP-1 | Growth Inhibition Assay | 0.25/0.5/1 μM | inhibits cell growth dose dependently | 23482748 | |
| HT1376 | Growth Inhibition Assay | IC50=1.88 ± 1.1 μM | 24054871 | ||
| T24 | Growth Inhibition Assay | IC50=1.37 ± 0.4 μM | 24054871 | ||
| UM-UC-3 | Growth Inhibition Assay | IC50=0.63 ±0.1 μM | 24054871 | ||
| SW620 | Growth Inhibition Assay | IC50=7.8 μM | 23542178 | ||
| SW480 | Growth Inhibition Assay | IC50=4.6 μM | 23542178 | ||
| SK-CO-1 | Growth Inhibition Assay | IC50=4 μM | 23542178 | ||
| LS-513 | Growth Inhibition Assay | IC50=3.9 μM | 23542178 | ||
| SW1116 | Growth Inhibition Assay | IC50=0.84 μM | 23542178 | ||
| LS-174T | Growth Inhibition Assay | IC50=0.84 μM | 23542178 | ||
| HCT 116 | Growth Inhibition Assay | IC50=0.41 μM | 23542178 | ||
| HCT 15 | Growth Inhibition Assay | IC50=0.3 μM | 23542178 | ||
| COLO 205 | Growth Inhibition Assay | IC50=0.24 μM | 23542178 | ||
| HT-29 | Growth Inhibition Assay | IC50=0.23 μM | 23542178 | ||
| COLO 201 | Growth Inhibition Assay | IC50=0.23 μM | 23542178 | ||
| Caco-2 | Growth Inhibition Assay | IC50=0.22 μM | 23542178 | ||
| SW48 | Growth Inhibition Assay | IC50=0.09 μM | 23542178 | ||
| SW-48 | Growth Inhibition Assay | IC50=0.1 μM | 22270257 | ||
| HCT-15 | Growth Inhibition Assay | IC50=0.3 μM | 22270257 | ||
| HCT 116 | Growth Inhibition Assay | IC50=0.6 μM | 22270257 | ||
| SW620-R | Growth Inhibition Assay | IC50=1.3 μM | 22270257 | ||
| SK-CO-1 | Growth Inhibition Assay | IC50=2.1 μM | 22270257 | ||
| SW620 | Growth Inhibition Assay | IC50=11 μM | 22270257 | ||
| BaF3 | Growth Inhibition Assay | GI50=1.449 μM | 22223645 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Torkinib (PP242) 是一种选择性的mTOR抑制剂，在无细胞试验中IC50为8 nM；靶向作用于mTOR复合体，作用于mTOR比作用于PI3Kδ或PI3Kα/β/γ选择性分别高10倍多和100倍。Torkinib (PP242) 可诱导线粒体自噬和凋亡。 | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| 特性 | 第一批以mTOR的ATP域为靶点的选择性抑制剂之一。 | ||||||||
| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | PP242作用于mTOR比作用于其他PI3K家族激酶，比如p110α，p110β，p110γ，p110δ，和DNA-PK(IC50分别为1.96 μM，2.2 μM，1.27 μM，0.102 μM，和0.408 μM)，表现出更有效的选择性。PP242对Ret，PKCα，PKCβ，和JAK2表现出一定的抑制活性，而对215种其他蛋白激酶具有显著的选择性。不同于rapamycin，PP242同时抑制mTORC1和 mTORC2。在BT549细胞中，PP242治疗(0.04-10 μM)以剂量依赖的方式抑制Akt，mTOR底物p70S6K，和其下游靶点S6的磷酸化。[1] PP242有效抑制PKCα，IC50 为49 nM。低浓度PP242抑制Akt S473磷酸化，较高浓度部分抑制除S473-P 外的Akt T308-P。PP242作为比rapamycin更有效的mTORC1抑制剂，能够抑制原代MEFs细胞的增殖，以及4EBP1在T36/45和S65上的磷酸化，比rapamycin更有效。通过比rapamycin引起更高水平的4EBP1 和eIF4E结合，PP242有效抑制cap依赖性翻译，而 rapamycin无此作用。[2] PP242有效抑制p190转化的小鼠BM，SUP-B15，和K562细胞增殖，GI50分别为12 nM，90 nM，和85 nM。PP242也会抑制固体肿瘤细胞系，如SKOV3，PC3，786-O，和U87的生长，GI50 分别为0.49 μM，0.19 μM，2.13 μM，和1.57 μM。[3] PP242能够比rapamycin更有效地使多发性骨髓瘤(MM)细胞减少和凋亡。[4] | |||
|---|---|---|---|---|
| 激酶实验 | 体外mTOR (FRAP1)激酶试验 | |||
| 重组mTOR与50-0.001 μM浓度范围内连续2倍稀释的PP242在试验缓冲液中进行培养，缓冲液包含50 mM HEPES，pH 7.5，1 mM EGTA，10 mM MgCl2，0.01% Tween，10 μM ATP (2.5 μCi of γ-32P-ATP)，和3 μg/mL BSA。大鼠重组PHAS-1/4EBP1 (2 mg/mL)用作底物。通过在1 M NaCl/1%磷酸(大约6次，每次5-10分钟)洗涤过的硝酸纤维素上点样终止反应。将板片干燥，转移的放射性通过磷光成像定量。IC50值使用Prism软件包将数据拟合到S形剂量反应曲线进行计算。 | ||||
| 细胞实验 | 细胞系 | MEFs | ||
| 浓度 | 在DMSO中溶解，终浓度为~10 μM | |||
| 孵育时间 | 72小时 | |||
| 方法 | 细胞用逐渐增加浓度的PP242在96孔板中处理72小时。处理72小时后，将10 μL 440 μM刃天青钠盐加入到每孔中，18小时后，每孔中的荧光强度使用顶端读取的荧光板阅读器在530 nm激发波长和590 nm发射波长下测量。 | |||
| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | p-mTOR / mTOR / p-AKT / AKT / p-S6 / S6 / p-4E-BP1 / 4E-BP-1 |
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23991179 | |
| Growth inhibition assay | Cell viability |
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23991179 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | 在小鼠脂肪和肝脏中，PP242给药能够完全抑制Akt在S473和T308的磷酸化。PP242仅部分抑制骨骼肌中Akt磷酸化，并且对T308磷酸化的抑制比对S473更有效，尽管其能够完全抑制4EBP1和S6的磷酸化。[2] PP242口服给药有效延缓白血病在小鼠模型中的发病，并通过抑制与细胞大小损失相关的mTORC2和mTORC1活化，诱导白血病消退。[3] PP242治疗有效抑制小鼠体内8226细胞的生长。[4] | |
|---|---|---|
| 动物实验 | Animal Models | 负荷小鼠p190转染的会引发白血病的BM细胞的同源(Balbc/J)小鼠，和静脉注射SUP-B15ffLuc细胞或人Ph+白血病细胞的雌性小鼠 |
| Dosages | ~60 mg/kg/day | |
| Administration | 口服强饲 | |
化学信息&溶解度
| 分子量 | 308.34 | 分子式 | C16H16N6O |
| CAS号 | 1092351-67-1 | SDF | Download Torkinib (PP242) SDF |
| Smiles | CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 61 mg/mL ( (197.83 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Water : Insoluble Ethanol : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）
mg/kg
g
μL
只
第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
计算结果：
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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常见问题及建议解决方法
问题 1:
Do you have any suggestions about potential candidates for vehicles that we could use for in vivo studies?
回答：
S2218 in the recommended solvent (30% PEG400 + 0.5% Tween80 + 5% Propylene glycol) is a suspension, and this formulation is for oral gavage. For IV injection, this compound can be dissolved in 2% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5mg/ml as a clear solution.
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