更新于：2024-11-01

TNK1

更新于：2024-11-01

基本信息

别名

CD38 negative kinase 1、KOS1、Non-receptor tyrosine-protein kinase TNK1

+ [3]

简介

Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction.

关联

项与 TNK1 相关的药物

TP-5809

靶点

TNK1

作用机制

TNK1抑制剂

在研机构

Sumitomo Dainippon Pharma Oncology, Inc.初创企业

原研机构

Sumitomo Dainippon Pharma Oncology, Inc.初创企业

在研适应症

肿瘤

非在研适应症

霍奇金淋巴瘤

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

TP-5801

靶点

TNK1

作用机制

TNK1抑制剂

在研机构-

原研机构

Sumitomo Pharma Co., Ltd. [+1]

在研适应症-

非在研适应症

肿瘤

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 TNK1 相关的临床结果

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100 项与 TNK1 相关的转化医学

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0 项与 TNK1 相关的专利（医药）

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133

项与 TNK1 相关的文献（医药）

2024-12-01·Journal of Reproductive Immunology

A loss of tuning of both pro-coagulant and inflammatory responses in monocytes in patients with preeclampsia

Article

作者: Saitoh, Shinichi ; Araki, Akemi ; Sabrina, Saima ; Asao, Hironobu ; Nagase, Satoru ; Nagashima, Mikako ; Takeda, Yuji

An imbalance between pro- and anti-angiogenesis is one of the leading causes of preeclampsia (PE). Monocytes, known as regulators of angiogenesis during immune responses, cooperate with platelets, but the specifics of these responses during pregnancy remain unclear. In this study, we investigated the relationship between pro-coagulant responses on monocytes [platelet activation marker CD61 as a monocyte-platelet aggregate (MPA), tissue factor (CD142), etc.], inflammatory responses [soluble CD40 ligand (sCD40L), soluble suppression of tumorigenesis-2 (sST2), etc.], and the balance of angiogenesis [soluble Fms-related receptor tyrosine kinase 1/placental growth factor (sFlt-1/PLGF) ratio]. In PE, markers of pro-coagulant and inflammatory responses were higher than those in normal pregnancy (NP). Interestingly, in NP, these markers harmonized with the sFlt-1/PLGF ratio, but not in PE. Furthermore, ex vivo examinations showed that upregulation of CD142 induced by additional platelet activation with adenosine diphosphate was diminished in PE. Conversely, low-dose aspirin, which is used as a preventive treatment for PE, could inhibit the increase of CD61 and sST2 under inflammatory stimuli and platelet activation in NP but not in PE. These results indicate that monocytes in PE upregulate basal activity and lose responsiveness to stimulation. The elevation of pro-coagulant and inflammatory responses may be mitigated by prophylaxis with low-dose aspirin. Therefore, the findings suggesting a loss of tuning of both pro-coagulant and inflammatory responses on monocytes help in understanding the pathology of PE. The harmonization between pro-coagulant responses, inflammatory responses, and angiogenesis may serve as useful indicators for the prediction and preventive treatment of PE.

2024-11-01·Drug Metabolism and Disposition

The Induction of Drug Uptake Transporter Organic Anion Transporting Polypeptide 1A2 by Radiation Is Mediated by the Nonreceptor Tyrosine Kinase v-YES-1 Yamaguchi Sarcoma Viral Oncogene Homolog 1

Article

作者: Wang, Xuyang ; Wu, Zicong ; Zhang, Ziqi ; Yuan, Jiajian ; Hong, Mei ; Li, Kui

Organic anion transporting polypeptides (OATP, gene symbol SLCO) are well-recognized key determinants for the absorption, distribution, and excretion of a wide spectrum of endogenous and exogenous compounds including many antineoplastic agents. It was therefore proposed as a potential drug target for cancer therapy. In our previous study, it was found that low-dose X-ray and carbon ion irradiation both upregulated the expression of OATP family member OATP1A2 and in turn, led to a more dramatic killing effect when cancer cells were cotreated with antitumor drugs such as methotrexate. In the present study, the underlying mechanism of the phenomenon was explored in breast cancer cell line MCF-7. It was found that the nonreceptor tyrosine kinase v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) was temporally coordinated with the change of OATP1A2 after irradiation. The overexpression of YES-1 significantly increased OATP1A2 both at the mRNA and protein level. The signal transducer and activator of transcription 3 (STAT3) pathway is likely the downstream target of YES-1 because phosphorylation and nuclear accumulation of STAT3 were both enhanced after overexpressing YES-1 in MCF-7 cells. Further investigation revealed that there are two possible binding sites of STAT3 localized at the upstream sequence of SLCO1A2, the encoding gene of OATP1A2. Electrophoretic mobility shift assay and chromatin immunoprecipitation analysis suggested that these two sites bound to STAT3 specifically and the overexpression of YES-1 significantly increased the association of the transcription factor with the putative binding sites. Finally, inhibition or knockdown of YES-1 attenuated the induction effect of radiation on the expression of OATP1A2. SIGNIFICANCE STATEMENT: The present study found that the effect of X-rays on v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1 (YES-1) and organic anion transporting polypeptides (OATP)1A2 was temporally coordinated. YES-1 phosphorylates and increases the nuclear accumulation of signal transducer and activator of transcription 3, which in turn binds to the upstream regulatory sequences of SLCO1A2, the coding gene for OATP1A2. Hence, inhibitors of YES-1 may suppress the radiation induction effect on OATP1A2.

2024-08-15·Heliyon

Harnessing rhizobacteria: Isolation, identification, and antifungal potential against soil pathogens.

Article

作者: Hussein, Safaa N ; Safaie, Naser ; Shams-Bakhsh, Masoud ; Al-Juboory, Hurria H

Rhizobacteria play a crucial role in plant health by providing natural antagonism against soil-borne fungi. The use of rhizobacteria has been viewed as an alternative to the use of chemicals that could be useful for the integrated management of plant diseases and also increase yield in an environmentally friendly manner. However, there is limited understanding of the specific mechanisms by which rhizobacteria inhibit these pathogens and the diversity of rhizobacterial species involved. This study aims to isolate, identify, and characterize rhizobacteria with antagonistic activities against soil-borne fungi. Laboratory tests were carried out on isolated rhizobacteria to evaluate their inhibitory activity against Rhizoctonia solani, Pythium aphanidermatum and Macrophomina phaseolina. The selected bacteria were identified using the Vitek 2 compact system and 16S rRNA genes. Experiments were carried out to evaluate the plant growth promotion and biocontrol ability of these selected isolates. Out of 324 rhizobacteria isolates obtained from various plant species, twelve were chosen due to their strong (>50 %) wide-ranging antifungal activity against three significant phytopathogenic fungi species. According to the identification results, they belong to the following species: Aeribacillus pallidus ECC4, Alloiococcus otitis BRE6, Aneurinibacillus thermoaerophilus ECL1, A. thermoaerophilus SDV1, Bacillus halotolerans DMC8, B. megaterium SKE2, B. megaterium TNK1, B. subtilis NAS1, Enterobacter cloacae complex BZD3, Leclercia adecarboxylata DKS3, Paenibacillus polymyxa TRS4, and Staphylococcus lentus BZD2. Eleven isolates produced protease, six isolates produced chitinase, and seven isolates were highly effective in producing hydrogen cyanide. Ten isolates could fix nitrogen, while all isolates could produce potassium, indole-3-acetic acid, siderophore, and ammonia. These findings enhance our understanding of rhizobacterial biodiversity and their potential as biocontrol agents in sustainable agriculture.