Tpl2 Kinase Inhibitor
(Synonyms: 4-[(3-氯-4-氟苯基)氨基]-6-[(3-吡啶甲基)氨基]-1,7-萘啶-3-甲腈) 目录号 : GC45067A Tpl2 inhibitor
Cas No.:871307-18-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tpl2 kinase inhibitor is a reversible inhibitor of tumor progression locus 2 (Tpl2; pIC50 = 7.3). It blocks LPS-induced TNF-α production in mice and human monocytes. Tpl2 kinase inhibitor has been used to evaluate the role of this enzyme in the proliferation and differentiation of cancer cells.
| Cas No. | 871307-18-5 | SDF | |
| 别名 | 4-[(3-氯-4-氟苯基)氨基]-6-[(3-吡啶甲基)氨基]-1,7-萘啶-3-甲腈 | ||
| Canonical SMILES | FC(C=C1)=C(Cl)C=C1NC2=C(C#N)C=NC(C=N3)=C2C=C3NCC4=CN=CC=C4 | ||
| 分子式 | C21H14ClFN6 | 分子量 | 404.8 |
| 溶解度 | DMF: 1 mg/ml,DMF:PBS(pH7.2) (1:2): 0.33 mg/ml,DMSO: 1 mg/ml | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4704 mL | 12.3518 mL | 24.7036 mL |
| 5 mM | 0.4941 mL | 2.4704 mL | 4.9407 mL |
| 10 mM | 0.247 mL | 1.2352 mL | 2.4704 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。
Tpl2 kinase impacts tumor growth and metastasis of clear cell renal cell carcinoma
Mol Cancer Res 2013 Nov;11(11):1375-86.PMID:23982215DOI:10.1158/1541-7786.MCR-13-0101-T.
Due to the innate high metastatic ability of renal cell carcinoma (RCC), many patients with RCC experience local or systemic relapses after surgical resection. A deeper understanding of the molecular pathogenesis underlying advanced RCC is essential for novel innovative therapeutics. Tumor progression locus 2 (Tpl2), upregulated in various tumor types, has been reported to be associated with oncogenesis and metastatic progression via activation of the MAPK signaling pathway. Herein, the relevance of Tpl2 in tumor growth and metastasis of RCC is explored. Inspection of The Cancer Genome Atlas (TCGA) indicated that Tpl2 overexpression was significantly related to the presence of metastases and poor outcome in clear cell RCC (ccRCC), which is the most aggressive subtype of RCC. Moreover, expression of Tpl2 and CXCR4 showed a positive correlation in ccRCC patients. Depletion of Tpl2 by RNAi or activity by a Tpl2 Kinase Inhibitor in human ccRCC cells remarkably suppressed MAPK pathways and impaired in vitro cell proliferation, clonogenicity, anoikis resistance, migration, and invasion capabilities. Similarly, orthotopic xenograft growth and lung metastasis were significantly inhibited by Tpl2 silencing. Furthermore, Tpl2 knockdown reduced CXCL12-directed chemotaxis and chemoinvasion accompanied with impaired downstream signaling, indicating potential involvement of Tpl2 in CXCR4-mediated metastasis. Taken together, these data indicate that Tpl2 kinase is associated with and contributes to disease progression of ccRCC. Implications: Tpl2 kinase activity has prognostic and therapeutic targeting potential in aggressive clear cell renal cell carcinoma.
TPL2 Kinase Is a Crucial Signaling Factor and Mediator of NKT Effector Cytokine Expression in Immune-Mediated Liver Injury
J Immunol 2016 May 15;196(10):4298-310.PMID:27053764DOI:10.4049/jimmunol.1501609.
Invariant NKT (iNKT) cells represent a subset of innate-like T lymphocytes that function as orchestrators of hepatic inflammation underpinning liver damage. In this study, we demonstrate that TPL2, an MAP3 kinase that has mostly been appreciated for its physiological role in macrophage responses, is a signaling factor in CD3(+)NK1.1(+) iNKT cells and mediator of hepatic inflammation. Genetic ablation of TPL2 in the mouse ameliorates liver injury induced by Con A and impinges on hallmarks of NKT cell activation in the liver without affecting NKT cell development in the thymus. The pivotal role of TPL2 in iNKT cell functions is further endorsed by studies using the iNKT-specific ligand α-galactosylceramide, which causes mild hepatitis in the mouse in a TPL2-dependent manner, including production of the effector cytokines IL-4 and IFN-γ, accumulation of neutrophils and licensing and activation of other immune cell types in the liver. A Tpl2 Kinase Inhibitor mirrors the effects of genetic ablation of TPL2 in vivo and uncovers ERK and Akt as the TPL2-regulated signaling pathways responsible for IL-4 and IFN-γ expression through the activation of the transcription factors JunB and NFAT. Collectively, these findings expand our understanding of the mechanisms of iNKT cell activation and suggest that modulation of TPL2 has the potential to minimize the severity of immune-driven liver diseases.
Tpl2 is a key mediator of arsenite-induced signal transduction
Cancer Res 2009 Oct 15;69(20):8043-9.PMID:19808956DOI:10.1158/0008-5472.CAN-09-2316.
Arsenite is a well-known human carcinogen that especially targets skin. The tumor progression locus 2 (Tpl2) gene encodes a serine/threonine protein kinase that is overexpressed in various cancer cells. However, the relevance of Tpl2 in arsenite-induced carcinogenesis and the underlying mechanisms remain to be explored. We show that arsenite increased Tpl2 kinase activity and its phosphorylation in mouse epidermal JB6 P+ cells in a dose- and time-dependent manner. Exposure to arsenite resulted in a marked induction of cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)), important mediators of inflammation and tumor promotion. Treatment with a Tpl2 Kinase Inhibitor or Tpl2 short hairpin RNA suppressed COX-2 expression and PGE(2) production induced by arsenite treatment, suggesting that Tpl2 is critical in arsenite-induced carcinogenesis. We also found that arsenite-induced phosphorylation of extracellular signal-regulated kinases (ERK) or c-Jun NH(2)-terminal kinases (JNK) was markedly suppressed by Tpl2 Kinase Inhibitor or Tpl2 short hairpin RNA. Inhibition of arsenite-induced ERK or JNK signaling using a pharmacologic inhibitor of ERK or JNK substantially blocked COX-2 expression. Furthermore, inhibition of Tpl2 reduced the arsenite-induced promoter activity of NF-kappaB and activator protein-1 (AP-1), indicating that NF-kappaB and AP-1 are downstream transducers of arsenite-triggered Tpl2. Our results show that Tpl2 plays a key role in arsenite-induced COX-2 expression and PGE(2) production and further elucidate the role of Tpl2 in arsenite signals that activate ERK/JNK and NF-kappaB/AP-1 in JB6 P+ cells.