更新于：2024-11-01

PP2A x Akt-1 x PI3K family

更新于：2024-11-01

基本信息

关联

项与 PP2A x Akt-1 x PI3K family 相关的药物

Sodium selenate

靶点

Akt-1 x PI3K family x PP2A

作用机制

Akt-1抑制剂 [+2]

在研机构

Monash University [+2]

原研机构

Velacor Therapeutics Pty Ltd.

在研适应症

额颞痴呆 [+3]

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

项与 PP2A x Akt-1 x PI3K family 相关的临床试验

ACTRN12623000446662 / Not yet recruiting临床2期

A Phase 2 Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Chronic Drug-resistant Temporal Lobe Epilepsy

开始日期2023-10-01

申办/合作机构

Alfred Health

ACTRN12620000236998 / Recruiting临床2期

A Phase 2b Randomised Controlled Trial of Sodium Selenate as a Disease Modifying Treatment for Possible Behavioural Variant Fronto-temporal Dementia

开始日期2021-08-17

申办/合作机构

Alfred Health

ACTRN12620001254987 / Recruiting临床2期

A Phase 2 Randomised Controlled Trial of Sodium Selenate as aDisease Modifying Treatment for Probable Progressive SupranuclearPalsy

开始日期2021-07-29

申办/合作机构

Alfred Health

100 项与 PP2A x Akt-1 x PI3K family 相关的临床结果

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100 项与 PP2A x Akt-1 x PI3K family 相关的转化医学

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0 项与 PP2A x Akt-1 x PI3K family 相关的专利（医药）

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项与 PP2A x Akt-1 x PI3K family 相关的文献（医药）

2020-11-01·Brain Research Bulletin3区 · 医学

FTY720 in CNS injuries: Molecular mechanisms and therapeutic potential

3区 · 医学

Review

作者: Wang, Handong ; Zhang, Li

Central nervous system (CNS) injuries, such as traumatic brain injury (TBI), subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), are important causes of disability and death worldwide. FTY720, a structural sphingosine analog and sphingosine-1-phosphate receptor (S1PR) modulator, is currently used in the treatment of relapsing-remitting multiple sclerosis (RRMS). However, recent in vivo and in vitro studies suggest that FTY720 plays a key role in many neurological diseases, especially in CNS injuries. In addition, FTY720 is under clinical trial for the treatment of acute stroke and ICH. FTY720 could exert anti-apoptosis, anti-inflammation and anti-oxidative stress effects in CNS injuries through different molecules and pathways such as sphingosine-1-phosphate receptor (S1PR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT), protein phosphatase 2A (PP2A) and P2 × 7 receptor (P2 × 7R). Thus, FTY720 shows great promise for the treatment of CNS injuries. This review covers a brief introduction about the relationship between FTY270 and CNS injuries, and an updated overview of downstream molecules of FTY720 in CNS injuries.

2020-02-01·Hepatology1区 · 医学

NAD(P)H Quinone Dehydrogenase 1 Ablation Inhibits Activation of the Phosphoinositide 3‐Kinase/Akt Serine/Threonine Kinase and Mitogen‐Activated Protein Kinase/Extracellular Signal‐Regulated Kinase Pathways and Blocks Metabolic Adaptation in Hepatocellular Carcinoma

1区 · 医学

Article

作者: Laknaur, Archana ; Humphries, Ashley ; Elattar, Sawsan ; Sharma, Ashok ; Satyanarayana, Ande ; Dimri, Manali ; Lee, Tae Jin ; Kolhe, Ravindra

Cancer cells undergo metabolic adaptation to sustain uncontrolled proliferation. Aerobic glycolysis and glutaminolysis are two of the most essential characteristics of cancer metabolic reprogramming. Hyperactivated phosphoinositide 3‐kinase (PI3K)/Akt serine/threonine kinase (Akt) and mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK) signaling pathways play central roles in cancer cell metabolic adaptation given that their downstream effectors, such as Akt and c‐Myc, control most of the glycolytic and glutaminolysis genes. Here, we report that the cytosolic flavoprotein, NAD(P)H quinone dehydrogenase 1 (Nqo1), is strongly overexpressed in mouse and human hepatocellular carcinoma (HCC). Knockdown of Nqo1 enhanced activity of the serine/threonine phosphatase, protein phosphatase 2A, which operates at the intersection of the PI3K/Akt and MAPK/ERK pathways and dephosphorylates and inactivates pyruvate dehydrogenase kinase 1, Akt, Raf, mitogen‐activated protein kinase kinase, and ERK1/2. Nqo1 ablation also induced the expression of phosphatase and tensin homolog, a dual protein/lipid phosphatase that blocks PI3K/Akt signaling, through the ERK/cAMP‐responsive element‐binding protein/c‐Jun pathway. Together, Nqo1 ablation triggered simultaneous inhibition of the PI3K/Akt and MAPK/ERK pathways, suppressed the expression of glycolysis and glutaminolysis genes and blocked metabolic adaptation in liver cancer cells. Conversely, Nqo1 overexpression caused hyperactivation of the PI3K/Akt and MAPK/ERK pathways and promoted metabolic adaptation. Conclusion: In conclusion, Nqo1 functions as an upstream activator of both the PI3K/Akt and MAPK/ERK pathways in liver cancer cells, and Nqo1 ablation blocked metabolic adaptation and inhibited liver cancer cell proliferation and HCC growth in mice. Therefore, our results suggest that Nqo1 may function as a therapeutic target to inhibit liver cancer cell proliferation and inhibit HCC.

2016-01-01·BioMed Research International3区 · 生物学

Cancerous Inhibitor of PP2A Silencing Inhibits Proliferation and Promotes Apoptosis in Human Multiple Myeloma Cells

3区 · 生物学

ArticleOA

作者: Yang, Xi ; Zhang, Yaping ; Liu, Hong ; Lin, Zenghua

Multiple myeloma is the second most prevalent type of blood cancer, representing approximately 1% of all cancers and 2% of all cancer deaths. There is therefore a strong need to identify critical targets in multiple myeloma neoplasia and progression. Cancerous inhibitor of PP2A (CIP2A) is a human oncoprotein that regulates cancer cell viability and anchorage-independent growth and induces apoptosis. The present study investigated CIP2A function in the human multiple myeloma cell lines RPMI-8226 and NCI-H929 to determine whether it can serve as a potential therapeutic target.CIP2Awas silenced in the cells by transfection of short interfering RNA and cell proliferation and apoptosis were evaluated by a tetrazolium salt-based assay and flow cytometry, respectively.CIP2Aknockdown inhibited proliferation and induced apoptosis in RPMI-8226 and NCI-H929 cells and decreased the phosphorylation of phosphoinositide 3-kinase (PI3K) p85, AKT1, and mammalian target of rapamycin (mTOR) without affecting total protein levels. Treatment ofCIP2A-depletion cells with insulin-like growth factor 1 decreased the effects ofCIP2Ainhibition on cell viability and apoptosis. These results indicate that CIP2A modulates myeloma cell proliferation and apoptosis via PI3K/AKT/mTOR signaling and suggest that it can potentially serve as a drug target for the treatment of multiple myeloma.