INK 128 (MLN0128)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
INK 128 (MLN0128)是一种选择性的mTOR抑制剂，IC50值为1 nM[3]。
哺乳动物雷帕霉素靶标（mTOR）蛋白是一种进化上保守的丝氨酸/苏氨酸激酶，参与PI3K / AKT / mTOR途径，在调控细胞生长和分裂的许多基本特征中起重要作用[1]。
INK 128 (MLN0128)是一种有效的额mTOR抑制剂。在人胰腺癌细胞中，INK-128以时间和浓度依赖的方式抑制mTOR，从而抑制细胞生长和存活[2]。在HER2阳性乳腺癌细胞系中，INK 128通过抑制mTOR显著延迟细胞周期，抑制细胞增殖[1]。
在ZR-75-1乳腺癌异种移植模型中，INK128以0.3 mg/kg/day的剂量给药后显著抑制肿瘤生长。当与其它标准的靶向治疗或化疗如sorafenib、sutent和paclitaxel组合治疗时增强了抗肿瘤生长的活性。据报道，INK128具有优良的理化性质，目前正在进行临床前评价[3]。在MDA-MB361小鼠模型中，INK 128给药20天后具有抗性，与lapatinib联合给药导致持久的肿瘤消退[1]。
参考文献：
[1]. Garcia-Garcia, C., et al., Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy. Clin Cancer Res, 2012. 18(9): p. 2603-12.
[2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8.
[3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.
- 1. Catherine DeMarino, Maria Cowen, et al. "Cannabinoids Reduce Extracellular Vesicle Release from HIV-1 Infected Myeloid Cells and Inhibit Viral Transcription." Cells. 2022 Feb 18;11(4):723. PMID:35203372
- 2. JLing NXY, Kaczmarek A, et al. "mTORC1 directly inhibits AMPK to promote cell proliferation under nutrient stress." Nat Metab. 2020 Jan;2(1):41-49. PMID:31993556
- 3. Matko Cancer, Hutter S, et al. "Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy." Cell Stem Cell. 2019 Nov 20. pii: S1934-5909(19)30426-6. PMID:31786016
- 4. Dong Q, Majumdar G, et al. "Insulin-induced de novo lipid synthesis occurs mainly via mTOR-dependent regulation of proteostasis of SREBP-1c." Mol Cell Biochem. 2019 Sep 20. PMID:31541353
- 5. Samluk L, Urbanska M, et al. "Cytosolic translational responses differ under conditions of severe short-term and long-term mitochondrial stress." Mol Biol Cell. 2019 Jul 15;30(15):1864-1877. PMID:31116686
- 6. Topf U, Suppanz I, et al. "Quantitative proteomics identifies redox switches for global translation modulation by mitochondrially produced reactive oxygen species." Nat Commun. 2018 Jan 22;9(1):324. PMID:29358734
- 7. Dite TA, Ling NXY, et al. "The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs." Nat Commun. 2017 Sep 18;8(1):571. PMID:28924239
- 8. Robert R. Redfield,Alonso Heredia,et al. "Treatment agents for inhibiting hiv and cancer in hiv infected patients." Google Patents.2016.
- 9. Heredia, Alonso, et al. "Targeting of mTOR catalytic site inhibits multiple steps of the HIV-1 lifecycle and suppresses HIV-1 viremia in humanized mice." Proceedings of the National Academy of Sciences (2015): 201511144. PMID:26170311
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 309.33 |
| Cas No. | 1224844-38-5 |
| Formula | C15H15N7O |
| Synonyms | INK128; INK-128 |
| Solubility | insoluble in H2O; ≥15.45 mg/mL in DMSO; ≥2.7 mg/mL in EtOH with gentle warming |
| Chemical Name | 5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine |
| SDF | Download SDF |
| Canonical SMILES | CC(C)N1C2=C(C(=N1)C3=CC4=C(C=C3)OC(=N4)N)C(=NC=N2)N |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 激酶实验 [1]: | |
|
激酶实验 |
使用LanthaScreen激酶试剂盒试剂测定mTOR活性。使用PI(3)KHTRF测定试剂盒测定PI(3)K α、β、γ和δ活性。使用20 μM ~ 0.1 nM的浓度（12点曲线）计算INK 128抑制50%酶活性所需的浓度 (IC50)。使用非线性回归模型测定IC50值。 |
| 细胞实验 [2]: | |
|
细胞系 |
PANC-1细胞 |
|
制备方法 |
在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液，一般步骤如下：请将试管置于37 °C加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20 °C可放置数月。 |
|
反应条件 |
10 ~ 100 nM；72小时 |
|
实验结果 |
INK 128呈时间和剂量依赖性地抑制PANC-1细胞存活。此外，在10 ~ 100 nM浓度下，INK 128显著降低PANC-1细胞活力。经INK 128处理48小时后显著降低细胞活力。 |
| 动物实验 [3]: | |
|
动物模型 |
ZR-75-1乳腺癌异种移植瘤模型 |
|
给药剂量 |
0.3 mg/kg/day；口服给药 |
|
实验结果 |
在ZR-75-1乳腺癌异种移植瘤模型中，INK 128显著抑制肿瘤生长。INK 128与其它标准靶向治疗或化疗（如：Sorafenib、Sutent和Paclitaxel）药物联合使用可以增强抗肿瘤生长活性。 |
|
其它注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
|
References: [1]. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012 Feb 22;485(7396):55-61. [2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8. [3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009. |
|
| 描述 | INK 128 (MLN0128)是一种有效的和选择性的mTOR抑制剂，IC50值为1 nM。 | |||||
| 靶点 | mTOR | PI3Kα | PI3Kγ | PI3Kδ | PI3Kβ | |
| IC50 | 1 nM (Ki=1.4 nM) | 219 nM | 221 nM | 230 nM | 5293 nM | |
质量控制和MSDS
- 批次:
化学结构
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