GW843682X(GW843682X) - 药物靶点：PLK1_专利_临床

概要

基本信息

药物类型

小分子化药

别名

GW 843682、GW 843682X、GW-843682

+ [3]

靶点

PLK1

作用机制

PLK1抑制剂(Polo样激酶1抑制剂)

治疗领域

肿瘤血液及淋巴系统疾病

在研适应症-

非在研适应症

急性髓性白血病肿瘤

原研机构

GSK Plc

在研机构-

非在研机构

GSK Plc

Université Fédérale Toulouse Midi-Pyrénées

最高研发阶段无进展临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C22H18F3N3O4S

InChIKeyJSKUWFIZUALZLX-UHFFFAOYSA-N

CAS号660868-91-7

关联

100 项与 GW843682X 相关的临床结果

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100 项与 GW843682X 相关的转化医学

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100 项与 GW843682X 相关的专利（医药）

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17

项与 GW843682X 相关的文献（医药）

2023-01-01·Mediators of inflammation

Comprehensive Analysis of the Expression, Prognostic Value, and Immune Infiltration Activities of GABRD in Colon Adenocarcinoma.

Article

作者: Wang, Jia-Xing ; Huang, Fakun ; Lin, Changqing ; Zhu, Liyue ; Wang, Zhengyang

Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one's treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients.

2023-01-01·Frontiers in immunology

Identification of a necroptosis-related gene signature as a novel prognostic biomarker of cholangiocarcinoma.

Article

作者: Gao, Xueping ; Xing, Jiyuan ; Guo, Zhixian ; Xu, Lixia

Background:

Cholangiocarcinoma (CHOL) is the most prevalent type of malignancy and the second most common form of primary liver cancer, resulting in high rates of morbidity and mortality. Necroptosis is a type of regulated cell death that appears to be involved in the regulation of several aspects of cancer biology, including tumorigenesis, metastasis, and cancer immunity. This study aimed to construct a necroptosis-related gene (NRG) signature to investigate the prognosis of CHOL patients using an integrated bioinformatics analysis.

Methods:

CHOL patient data were acquired from the Gene Expression Omnibus (GEO) (GSE89748, GSE107943) and The Cancer Genome Atlas (TCGA) databases, with NRGs data from the necroptosis pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Univariate and multivariate regression analyses were performed to establish the NRG signatures. Kaplan-Meier (KM) curves were used to evaluate the prognosis of patients with CHOL. Functional enrichment analysis was performed to identify key NRG-associated biological signaling pathways. We also applied integrative multi-omics analysis to the high- and low-risk score groups. Spearman's rank correlation was used to clarify the relationship between the NRG signature and immune infiltration.

Results:

65 differentially expressed (DE) NRGs were screened, five of which were selected to establish the prognostic signature of NRG_S based on multivariate Cox regression analysis. We observed that low-risk patients survived significantly longer than high-risk patients. We found that patients with high-risk scores experienced higher immune cell infiltration, drug resistance, and more somatic mutations than patients with low-risk scores. We further found that sensitivities to GW843682X, mitomycin C, rapamycin, and S-trityl-L-cysteine were significantly higher in the low-risk group than in the high-risk group. Finally, we validated the expression of five NRGs in CHOL tissues using the TCGA database, HPA database and our clinical data.

Conclusion:

These findings demonstrate that the five-NRG prognostic signature for CHOL patients is reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of CHOL patients in the future.

2017-09-12·Anti-cancer agents in medicinal chemistry4区 · 医学

Polo-Like Kinase 1 Pharmacological Inhibition as Monotherapy or in Combination: Comparative Effects of Polo-Like Kinase 1 Inhibition in Medulloblastoma Cells

4区 · 医学

Article

作者: Scrideli, Carlos Alberto ; Brassesco, Maria Sol ; Ramos, Priscila Maria Manzini ; Tone, Luiz Gonzaga ; Pezuk, Julia Alejandra

BACKGROUND:

Medulloblastoma (MB) is one of most frequent malignant tumors that affect children. Despite the relatively good survival rate, long time sequels still represent a challenge for MB. Therefore, in an attempt to reduce treatment aftereffects, new therapeutic targets are constantly being explored. Polo like kinase 1 (PLK1) is a master cell cycle regulator that is increased in proliferative cells, while its depletion has been repeatedly proposed as an oncological therapeutic strategy.

OBJECTIVES:

Here, we evaluated and compared the effects of PLK1 inhibition alone and in combination with currently used radio- and chemotherapy in MB cells.

METHODS:

UW402, UW473, ONS-76 and DAOY MB cell lines were treated with BI 2536, BI 6727, GW843682X, and GSK461364 PLK1 inhibitors and cell proliferation, apoptosis, clonogenicity, cell invasion, adhesion and cell cycle distribution were evaluated. In addition, the combinatorial effect with gamma irradiation or etoposide, cisplatin and temozolomide was evaluated.

RESULTS:

We show that PLK1 inhibition causes a significant decrease on cell proliferation, clonogenic capacity, cell invasion and adhesion, with modest differences between inhibitors. Yet, the four drugs cause G2/M arrest followed by increased cell death. PLK1 inhibition proved to be efficient to sensitize MB cells to radiation irrespective of the inhibitor, even though it showed thrifty results when combined with chemotherapy.

CONCLUSIONS:

We proved that all PLK1 inhibitors have anti-mitotic effects on MB cells, supporting the idea of using them as radiosensitizers. Taken together, our results strengthen the potential of using PLK1 as a therapeutic target to improve treatment strategy for this tumor.

100 项与 GW843682X 相关的药物交易

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