Last update 01 Nov 2024

SIRT1 x p53 x Notch-1

Last update 01 Nov 2024

Basic Info

Related Targets

SIRT1p53Notch-1

Drugs associated with SIRT1 x p53 x Notch-1

AG-1031

Target

Notch-1 x SIRT1 x p53

Mechanism

NOTCH1 inhibitors [+2]

Active Org.

Ascentgene, Inc. As

Originator Org.

Ascentgene, Inc. As

Active Indication

Glioma [+1]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SIRT1 x p53 x Notch-1

ChiCTR2300071526 / SuspendedEarly Phase 1IIT

A prospevtive clinical study of the prediction and early diagnosis for preeclampsia based on SIRT1

Start Date01 Jun 2023

Sponsor / Collaborator-

NCT01158300 / CompletedPhase 1IIT

Phase I and Pharmacokinetic Trial of PTC299 in Pediatric Patients With Refractory or Recurrent CNS Tumors

RATIONALE: PTC299 may stop the growth of tumor cells by blocking blood flow to the tumor.
PURPOSE: This phase I trial is studying the side effects and the best dose of PTC299 in treating young patients with recurrent or refractory primary central nervous system tumors.

Start Date01 Nov 2010

Sponsor / Collaborator

PTC Therapeutics, Inc.

[+1]

100 Clinical Results associated with SIRT1 x p53 x Notch-1

100 Translational Medicine associated with SIRT1 x p53 x Notch-1

0 Patents (Medical) associated with SIRT1 x p53 x Notch-1

Literatures (Medical) associated with SIRT1 x p53 x Notch-1

31 Mar 2021·Radiation Oncology Journal

Exploring the differentially expressed genes in human lymphocytes upon response to ionizing radiation: a network biology approach

Article

Author: Gollapalli, Pavan ; Kedilaya, Vishakh R ; Shetty, Praveenkumar ; Sekaran, Tamizh Selvan Gnana ; Kumari, Suchetha N

PURPOSEThe integration of large-scale gene data and their functional analysis needs the effective application of various computational tools. Here we attempted to unravel the biological processes and cellular pathways in response to ionizing radiation using a systems biology approach.MATERIALS AND METHODSAnalysis of gene ontology shows that 80, 42, 25, and 35 genes have roles in the biological process, molecular function, the cellular process, and immune system pathways, respectively. Therefore, our study emphasizes gene/protein network analysis on various differentially expressed genes (DEGs) to reveal the interactions between those proteins and their functional contribution upon radiation exposure.RESULTSA gene/protein interaction network was constructed, which comprises 79 interactors with 718 interactions and TP53, MAPK8, MAPK1, CASP3, MAPK14, ATM, NOTCH1, VEGFA, SIRT1, and PRKDC are the top 10 proteins in the network with high betweenness centrality values. Further, molecular complex detection was used to cluster these associated partners in the network, which produced three effective clusters based on the Molecular Complex Detection (MCODE) score. Interestingly, we found a high functional similarity from the associated genes/proteins in the network with known radiation response genes.CONCLUSIONThis network-based approach on DEGs of human lymphocytes upon response to ionizing radiation provides clues for an opportunity to improve therapeutic efficacy.

01 Aug 2020·Vascular PharmacologyQ3 · MEDICINE

Indoxyl sulfate promotes the atherosclerosis through up-regulating the miR-34a expression in endothelial cells and vascular smooth muscle cells in vitro

Q3 · MEDICINE

Article

Author: Li, Xiaowei ; Yang, Yaolin ; Jin, Wen ; Zhou, Fenghua ; Zhao, Yiqiao ; Lu, Zibin ; Chen, Sen ; Xie, Zhiqiu

Atherosclerosis (AS) is one of the most common cardiovascular events in patients with chronic renal insufficiency (CRI). During the development of CRI, uremic toxins, including indoxyl sulfate (IS), are pivotal risk factors for AS. However, the underlying mechanism between AS and IS has not been fully elucidated. The present study was designed to test our hypothesis that IS promotes the AS by regulating viability, proliferation, migration and apoptosis of endothelial cells and vascular smooth muscle cells. In this present study, our date showed that IS inhibited the cell viability of human umbilical vein endothelial cells (HUVECs) and human aortic vascular smooth muscle cells (HA-VSMCs) in a dose-dependent manner (P < .05). Moreover, IS inhibited the proliferation, migration and induced apoptosis of HUVECs and HA-VSMCs significantly (P < .05). However, inhibition of the miR-34a abolished these effects of IS in vitro, indicating that miR-34a is involved in the development of AS induced by IS. In addition, the luciferase reporter gene assay showed that up-regulating of miR-34a inhibited the Notch1 transcriptional activity remarkably (P < .05). The expression of Notch1 decreased after IS treatment, while miR-34a inhibitor attenuated this effect. Moreover, the expression of miR-34a-related proteins Wnt-1, Jag1, E2F1 and SIRT1 decreased, while the expression of p53 increased in HUVECs and HA-VSMCs after IS treatment. Consistently, blockage of miR-34a abolished the remarkable effects on protein expressions induced by IS. Taken together, this study showed that IS can inhibit the proliferation, migration and promote apoptosis of HUVECs and HA-VSMCs through the Notch1 signal and miR-34a-related proteins by up-regulating miR-34a. These findings may provide new insights into the underlying mechanism of AS in CRI.

01 Jun 2020·Anticancer ResearchQ4 · MEDICINE

Sirtuin 1 Activation Suppresses the Growth of T-lymphoblastic Leukemia Cells by Inhibiting NOTCH and NF-κB Pathways

Q4 · MEDICINE

Article

Author: Okasha, Salwa M ; Itoh, Mai ; Tohda, Shuji

BACKGROUND/AIMThe deacetylase sirtuin1 (SIRT1) inhibits tumor suppressor p53 and may promote tumorigenesis; however, SIRT1 effects on leukemia cells are controversial. The aim of this study was to clarify the activity of SIRT1 in leukemia cells.MATERIALS AND METHODSThe effects of SIRT1 inhibition or activation and SIRT1 knockdown or overexpression were examined in two T cell acute lymphoblastic leukemia (T-ALL) cell lines carrying NOTCH1 mutations and three acute myeloid leukemia (AML) cell lines.RESULTSThe growth of T-ALL cells was promoted by SIRT1 inhibition and SIRT1 knockdown but was reduced by SIRT1 activation and overexpression; however, no effects were observed in AML cells. SIRT1 activation decreased NOTCH, NF-κB, and mTOR signaling and inhibited p53, suggesting that the possible mechanisms of T-ALL growth suppression by SIRT1 are independent of p53.CONCLUSIONSIRT1 activators acting through the down-regulation of NOTCH, NF-κB, and mTOR pathways can be novel targeted drugs for NOTCH1-mutated T-ALLs.

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