OSU-T315 (ILK-IN-1)
(Synonyms: OSU-T315 analog) 目录号 : GC32731
An ILK inhibitor
Cas No.:1333146-24-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
ILK-IN-2 is an inhibitor of integrin-linked kinase (ILK; IC50 = 0.6 ?M).1 It inhibits the phosphorylation of Akt, glycogen synthase kinase 3β (GSK3β), and myosin light-chain (MLC) in PC3 prostate and MDA-MB-231 breast cancer cells when used at concentrations ranging from 1 to 4 ?M. ILK-IN-2 inhibits the proliferation of LNCaP, PC3, MDA-MB-231, MDA-MB-468, SK-BR-3, and MCF-7 cancer cells (IC50s = 1.6, 2, 1, 1.5, 1.8, and 2.5 ?M, respectively), as well as induces autophagy and apoptosis in PC3 cells when used at a concentration of 2 ?M. It also reduces protein levels of Y-box binding protein (YB-1), HER2, and EGFR in PC3 cells. ILK-IN-2 (25 and 50 mg/kg) reduces tumor growth in a PC3 mouse xenograft model.
1.Lee, S.-L., Hsu, E.-C., Chou, C.-C., et al.Identification and characterization of a novel integrin-linked kinase inhibitorJ. Med. Chem.54(18)6364-6374(2011)
| Cas No. | 1333146-24-9 | SDF | |
| 别名 | OSU-T315 analog | ||
| Canonical SMILES | O=C(NC)CCC1=NN(C2=CC=C(N3CCNCC3)C=C2)C(C4=CC=C(C5=CC=C(C(F)(F)F)C=C5)C=C4)=C1 | ||
| 分子式 | C30H30F3N5O | 分子量 | 533.59 |
| 溶解度 | DMSO : ≥ 50 mg/mL (93.70 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8741 mL | 9.3705 mL | 18.741 mL |
| 5 mM | 0.3748 mL | 1.8741 mL | 3.7482 mL |
| 10 mM | 0.1874 mL | 0.937 mL | 1.8741 mL |
| 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） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
OSU-T315 and doxorubicin synergistically induce apoptosis via mitochondrial pathway in bladder cancer cells
Cell Biol Int 2022 Oct;46(10):1672-1681.PMID:35830716DOI:10.1002/cbin.11855.
Bladder cancer (BC) is a common urological malignancy that still lacks an effective treatment. Doxorubicin (Dox) has been widely used in the treatment of various cancers, including BC. However, chemoresistance often hampers the clinical application of Dox, therefore, it is necessary to develop effective strategies to improve its efficacy. By using high-throughput screening, we identified OSU-T315, an integrin-linked kinase (ILK) inhibitor, that can augment the cytotoxicity of Dox against BC cells. We found that OSU-T315 and Dox synergistically induce apoptosis of BC cells via mitochondrial pathway in a caspase-dependent. Mechanically, it was found that OSU-T315 and Dox synergistically induced activation of Bax which is critical for the induction of apoptosis. Moreover, it was also found that the downregulation of BCL-2 and MCL-1 is essential for the activation of BAX induced by OSU-T315 and Dox. OSU-T315 was found to downregulate MCL-1 via the GSK-3β/FBXW7 axis in BC cells. Our findings suggest that combined treatment with OSU-T315 and Dox may be a promising strategy to treat BC.
The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation
Austin J Med Oncol 2016;3(1):1025.PMID:27642646doi
Activation of PKB/AKT signaling, which requires PDK1 and PDK2 function, drives Vestibular Schwannoma (VS) and meningioma growth. PDK2 function is defined as a molecule that phosphorylates AKT-Ser473. Integrin-Linked Kinase (ILK) functions as PDK2 in PKB/AKT activation in many cancers; therefore, we hypothesized that OSU-T315, a small molecule ILK inhibitor, will inhibit the ILK-PDK2 function in PKB/AKT signaling activation in VS and meningioma cell growth. OSU-T315 decreased cell viability at IC50 < 2μM in VS (HEI193) and meningioma (Ben-Men-1) cell lines, in primary cells at < 3.5μM, while in normal primary Schwann cells at 7.1μM. OSU-T315 inhibits AKT signaling by decreasing phosphorylation at AKT-Ser473, AKT-Thr308, ILK-Ser246 and ILK-Thr173. In addition, OSU-T315 affected the phosphorylation or expression levels of AKT downstream proliferation effectors as well as autophagy markers. Flow cytometry shows that OSU-T315 increased the percentage of cells arrested at G2/M for both, HEI193 (39.99%) and Ben-Men-1 (26.96%) cells, compared to controls (21.54%, 8.47%). Two hours of OSU-T315 treatment increased cell death in both cell lines (34.3%, 9.1%) versus untreated (12.1%, 8.1%). Though longer exposure increased cell death in Ben-Men-1, TUNEL assays showed that OSU-T315 does not induce apoptosis. OSU-T315 was primarily cytotoxic for HEI193 and Ben-Men-1 inducing a dysregulated autophagy. Our studies suggest that OSU-T315 has translational potential as a chemotherapeutic agent against VS and meningioma.
OSU-T315 as an Interesting Lead Molecule for Novel B Cell-Specific Therapeutics
J Immunol Res 2018 Sep 12;2018:2505818.PMID:30276218DOI:10.1155/2018/2505818.
B cells are pathogenic in various disease processes and therefore represent an interesting target for the development of novel immunosuppressants. In the search for new therapeutic molecules, we utilized an in vitro B cell activation assay with ODN2006-stimulated Namalwa cells to screen a chemical library of small molecules for B cell modulating effects. OSU-T315, described as an inhibitor of integrin-linked kinase (ILK), was hereby identified as a hit. On human and murine primary B cells, OSU-T315 potently suppressed the proliferation and the production of antibodies and cytokines upon stimulation, suggesting that ILK could be a promising target in the modulation of B cell activity. Mice with B cell-specific knockout of ILK were generated. Surprisingly, knockout of ILK in murine B cells did not affect B cell function as assessed by several in vivo and ex vivo B cell assays and did not alter the B cell immunosuppressive activity of OSU-T315. In conclusion, OSU-T315 displays potency as B cell modulator, probably through a mechanism of action independent of ILK, and might serve as lead drug molecule for the development of novel B cell-selective drugs.
OSU-T315: a novel targeted therapeutic that antagonizes AKT membrane localization and activation of chronic lymphocytic leukemia cells
Blood 2015 Jan 8;125(2):284-95.PMID:25293770DOI:10.1182/blood-2014-06-583518.
Aberrant regulation of endogenous survival pathways plays a major role in progression of chronic lymphocytic leukemia (CLL). Signaling via conjugation of surface receptors within the tumor environmental niche activates survival and proliferation pathways in CLL. Of these, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway appears to be pivotal to support CLL pathogenesis, and pharmacologic inhibitors targeting this axis have shown clinical activity. Here we investigate OSU-T315, a compound that disrupts the PI3K/AKT pathway in a novel manner. Dose-dependent selective cytotoxicity by OSU-T315 is noted in both CLL-derived cell lines and primary CLL cells relative to normal lymphocytes. In contrast to the highly successful Bruton's tyrosine kinase and PI3K inhibitors that inhibit B-cell receptor (BCR) signaling pathway at proximal kinases, OSU-T315 directly abrogates AKT activation by preventing translocation of AKT into lipid rafts without altering the activation of receptor-associated kinases. Through this mechanism, the agent triggers caspase-dependent apoptosis in CLL by suppressing BCR, CD49d, CD40, and Toll-like receptor 9-mediated AKT activation in an integrin-linked kinase-independent manner. In vivo, OSU-T315 attains pharmacologically active drug levels and significantly prolongs survival in the TCL1 mouse model. Together, our findings indicate a novel mechanism of action of OSU-T315 with potential therapeutic application in CLL.
GDC-0941 activates integrin linked kinase (ILK) expression to cause resistance to GDC-0941 in breast cancer by the tumor necrosis factor (TNF)-α signaling pathway
Bioengineered 2022 Apr;13(4):10944-10955.PMID:35477364DOI:10.1080/21655979.2022.2066758.
Breast cancer is characterized by high morbidity and mortality. GDC-0941 is a PI3K inhibitor with oncogenic effects in breast cancer. However, certain breast cancer cells are insensitive to GDC-0941. Hence, the mechanism of GDC-0941 in breast cancer resistance was investigated in this study. Breast cancer cell lines BT-474, MCF7, Hs-578-T, MDA-MB-231, MDA-MB-453, and MDA-MB-468 were cultured in different medium and then treated with 100 or 500 nM GDC-0941, 100 nM OSU-T315, or TNF-α antibody. Moreover, ILK and shILK were transfected into cells. The half maximal inhibitory concentrations (IC50) for GDC-0941 were detected using CCK-8 assay. The levels of ILK, AKT, PDK1, S6, and p70S6K expression were detected using western blotting and qPCR. In addition, the mouse model of breast cancer was constructed to measure the tumor size, volume, and weight. The results showed that GDC-0941 decreased cell survival rate, downregulated the phosphorylation of AKT, S6, and p70S6K, and promoted the expression of ILK, while it had little effect on PDK1 expression. GDC-0941 inhibited the increases in p-AKT, p-S6, and p-p70S6K caused by ILK overexpression and promoted ILK knockdown-induced reduction of p-AKT, p-S6, and p-p70S6K. In addition, the combination of OSU-T315 and GDC-0941 decreased p-AKT, p-S6, and p-p70S6K level, tumor volume, and tumor weight. GDC-0941 promoted ILK expression by upregulating TNF-α level. Taken together, GDC-0941 increased ILK level by upregulating TNF-α, thus affecting AKT expression and the sensitivity of breast cancer cells to GDC-0941.