更新于：2024-11-01

Ral GTP酶

更新于：2024-11-01

基本信息

别名-

简介-

关联

项与 Ral GTP酶相关的药物

RAL inhibitor (PHusis Therapeutics)

靶点

Ral GTP酶

作用机制

Ral GTP酶抑制剂

在研机构

Phusis Therapeutics, Inc.

原研机构

Phusis Therapeutics, Inc.

在研适应症

肿瘤

非在研适应症-

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

100 项与 Ral GTP酶相关的临床结果

登录后查看更多信息

100 项与 Ral GTP酶相关的转化医学

登录后查看更多信息

0 项与 Ral GTP酶相关的专利（医药）

登录后查看更多信息

项与 Ral GTP酶相关的文献（医药）

2024-10-01·Journal of Thrombosis and Haemostasis

Critical role for platelet Ral GTPases in regulating venous thrombosis in mice

Article

作者: Williams, Christopher M. ; Poole, Alastair W. ; Poole, Alastair W ; Furniss, Jonathan A. ; Li, Yong ; Walsh, Tony G. ; Amulic, Borko ; Brill, Alexander ; Williams, Christopher M ; Walsh, Tony G ; Vautrinot, Jordan ; Furniss, Jonathan A

BACKGROUNDDeep vein thrombosis (DVT) is a major cause of morbidity and mortality globally. While its pathophysiology is complex, increasing evidence suggests a more prominent role for platelets than previously suspected. Genetic deletion of Ral GTPases, RalA and RalB, conditionally in mouse platelets (RalAB DKO), results in a near complete defect in P-selectin externalisation upon activation, while other platelet activation responses and arterial thrombosis are preserved.OBJECTIVEGiven the critical role of P-selectin in mediating platelet-neutrophil interaction and thromboinflammation, we sought to investigate whether platelet Rals would also play critical roles in venous thrombosis, a thromboinflammatory disease, using RalAB DKO mice.METHODSDVT was induced by surgical partial ligation of the caudal (inferior) vena cava for 24-h or 48-h before venous thrombi were assessed by histology and immunofluorescence microscopy.RESULTSRalAB DKO mice show a reduction in venous thrombus formation after 24-h, and near complete ablation of venous thrombosis by 48-h post IVC ligation. Immunofluorescence microscopy revealed that cross sections of thrombi from wildtype mice consist of an organised scaffolded structure of platelets surrounding leukocytes/neutrophils producing NETs to stabilize and propagate the thrombus. This organised structure was absent in platelet-specific conditional RalAB DKO thrombi. In vitro analysis of platelet-mediated NET formation was also significantly reduced when platelets lacked RalAB or when platelets were treated with the Ral inhibitor RBC8.CONCLUSIONWe identify platelet Rals as novel, potentially critical regulators of venous thrombus stability, through their ability to regulate neutrophil NET formation via platelet P-selectin.

2015-07-03·Small GTPases

Drugging the Ral GTPase

Article

作者: Yan, Chao ; Jones, David NM ; Theodorescu, Dan

The RAL GTPases have emerged as important drivers of tumor growth and metastasis in lung, colon, pancreatic and other cancers. We recently developed the first small molecule inhibitors of RAL that exhibited antitumor activity in human lung cancer cell lines. These compounds are non-competitive inhibitors that bind to the allosteric site of GDP-bound RAL. The RAL inhibitors have the potential to be used in combination therapy with other inhibitors of the RAS signaling pathway. They also provide insights toward directly targeting other GTPases.

2002-10-24·Oncogene1区 · 医学

Involvement of R-Ras and Ral GTPases in estrogen-independent proliferation of breast cancer cells

1区 · 医学

Article

作者: Yi Yu ; Larry A Feig

A key step in the progression of breast cancer is the conversion of cells from an estrogen-dependent to an estrogen-independent state. Yet the molecular mechanisms underlying this transition in the control of cell proliferation of breast cancer cells remain poorly understood. A potential role for Ras-related GTPases in this process was suggested by the finding that BCAR3/AND-34, a protein isolated on the basis of its ability to convert MCF-7 and ZR-75 breast cancer cell lines to estrogen independence and tamoxifen resistance, is a guanine nucleotide exchange factor with the potential to activate the Ras-related Ral, R-Ras and Rap GTPases. In this study we investigated the potential contribution of these GTPases to the generation of estrogen-independence in MCF-7 cells. We found that elevated R-Ras but not Ral or Rap activity was sufficient to induce estrogen-independent proliferation of MCF-7 cells. The effect of R-Ras was dependent upon its ability to constitutively activate the AKT kinase. Interestingly, although AKT was also constitutively activated when estrogen-independent proliferation was induced by over-expression of EGF receptors, this mechanism of hormone independence did not require AKT activation. In contrast, EGF receptors did require Ral activation to induce estrogen-independent proliferation, while Ral activation was not required for estrogen-induced proliferation of MCF-7 cells. These findings suggest that Ral activity takes on a significant role in controlling cell proliferation of breast cancer cells when progression to estrogen-independence is associated with over-expression of EGF receptor family members. Moreover, because R-Ras promotes hormone-independent growth in a manner distinct from EGF receptors, it may participate in the conversion of breast cancer cells to estrogen independence when over-expression of EGF receptor family members is not involved.