An Open-label Study to Investigate the Safety, Tolerability and Efficacy of a Single 6-hour Intravenous Infusion of AMO-01 to Treat Adolescents and Adults With Phelan-McDermid Syndrome (PMS) and Co-morbid Epilepsy

The purpose of this study is to investigate the safety, tolerability and efficacy of a single 6-hour intravenous infusion of AMO-01 to treat adolescents and adults with PMS and co-morbid epilepsy. Phelan-McDermid Syndrome (PMS) is a neurodevelopmental disorder characterized by a chromosomal deletion or mutation at 22q13.3 that contains the SHANK3/ProSAP2 gene. A key co-morbidity in PMS is the presence of epilepsy. Currently there are no approved treatments for PMS. Furthermore, there has been relatively little clinical study of pharmacological interventions for PMS. AMO-01 may provide benefit to PMS patients exhibiting behavioral abnormalities and seizures.

开始日期2018-05-30

申办/合作机构

Icahn School of Medicine at Mount Sinai

NCT00730262 / Terminated临床2期

A Phase II Study of TLN-4601 in Patients With Glioblastoma Multiforme

The objective of this study is to assess the efficacy and safety of TLN-4601 used to treat patients with Glioblastoma Multiforme(GBM) that recur/progress after receiving first line systemic therapy post surgery/radiotherapy.

开始日期2008-08-01

申办/合作机构

Thallion Pharmaceuticals, Inc.

NCT00338026 / Completed临床1期

A Phase I, Dose Finding, Pharmacokinetic, and Safety Study of Continuous IV Infusion of ECO-4601 in Patients With Advanced Cancer Including an Extension Portion to Obtain Safety Data at the Highest Tolerable Dose

The purpose of this study was to determine the maximum tolerated dose (MTD) and the recommended dose for future studies of ECO-4601 administered as a continuous IV infusion for 14 days with 7 days recovery (21 day cycle) in patients with histologically confirmed solid tumors (high grade glioma, colorectal, lung, breast, ovarian, pancreatic and prostate). This study was also designed to determine the clinical pharmacokinetic profile, safety of multiple cycles of administration, and document the antitumor activity of ECO-4601.

开始日期2006-02-01

申办/合作机构

Thallion Pharmaceuticals, Inc.

100 项与 RAS x TSPO 相关的临床结果

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100 项与 RAS x TSPO 相关的转化医学

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0 项与 RAS x TSPO 相关的专利（医药）

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项与 RAS x TSPO 相关的文献（医药）

2023-07-01·Iranian journal of public health

Inhibiting the Proliferation of Colorectal Cancer Cells by Reducing TSPO/VDAC Expression.

Article

作者: Wang, Shuyue ; Yang, Weining ; Liu, Yang

BackgroundWe aimed to explore the mechanism of the effect of remimazolam (Rem) on the proliferation of colorectal cancer (CRC) cells with CRC as a disease context.MethodsTranslocation protein (TSPO) expression in CRC was determined by Western blotting and qRT-PCR in the Second Affiliated Hospital of Qiqihar Medical University from March 2019 to February 2022. TSPO-interacting proteins were predicted through string database. The proliferation was measured by CCK-8 and 5-ethynyl-2-deoxyuridine (EDU). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) and clonal colony on cells were formed to screen for the optimal concentration of Rem and to detect the viability. The expression of apoptosis-related proteins, Bcl-2 and P53, was determined by qRT-PCR and Western blotting. The effect of Rem on the expression of tumor markers, CEA and CA19-9, in CRC was examined through ELISA.ResultsTSPO expression in CRC tissues and cells was higher than that in ANT samples and normal intestinal epithelial cells. Over-expression of TSPO promoted the proliferation of HCT116 and the expression of tumor markers CEA and CA19-9 and inhibited the apoptosis of HCT116. Interference with TSPO inhibited the proliferation of HCT116 and the expression of CEA and CA19-9 and promoted the apoptosis of HCT116. 1 μg/mL Rem could inhibit the viability of HCT116, the proliferation of HCT116 and the expression of CEA and CA19-9, and improve the apoptosis of HCT116. TSPO could interact with VDAC and affect its protein expression, and Rem could inhibit the proliferation and the expression of CEA and CA19-9 through the TSPO/VDAC pathway, to promote its apoptosis.ConclusionRem affects the proliferation of CRC cells by inhibiting the TSPO/VDAC pathway.

2023-04-21·Hereditas

Identification and validation of autophagy-related genes in Kawasaki disease.

Article

作者: Zhu, Hao ; Liao, Qing ; Li, Aimin ; Xu, Biao ; Hu, Cunshu

BACKGROUNDKawasaki disease (KD) is a systemic vasculitis of unknown etiology affecting mainly children. Studies have shown that the pathogenesis of KD may be related to autophagy. Using bioinformatics analysis, we assessed the significance of autophagy-related genes (ARGs) in KD.METHODSCommon ARGs were identified from the GeneCards Database, the Molecular Signatures Database (MSigDB), and the Gene Expression Omnibus (GEO) database. ARGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction (PPI) network analysis. Furthermore, related microRNAs (miRNAs), transcription factors (TFs), and drug interaction network were predicted. The immune cell infiltration of ARGs in tissues was explored. Finally, we used receiver operating characteristic (ROC) curves and quantitative real-time PCR (qRT-PCR) to validate the diagnostic value and expression levels of ARGs in KD.RESULTSThere were 20 ARGs in total. GO analysis showed that ARGs were mainly rich in autophagy, macro-autophagy, and GTPase activity. KEGG analysis showed that ARGs were mainly rich in autophagy-animal and the collecting duct acid secretion pathway. The expression of WIPI1, WDFY3, ATP6V0E2, RALB, ATP6V1C1, GBA, C9orf72, LRRK2, GNAI3, and PIK3CB is the focus of PPI network. A total of 72 related miRNAs and 130 related TFs were predicted by miRNA and TF targeting network analyses. Ten pairs of gene-drug interaction networks were also predicted; immune infiltration analysis showed that SH3GLB1, ATP6V0E2, PLEKHF1, RALB, KLHL3, and TSPO were closely related to CD8 + T cells and neutrophils. The ROC curve showed that ARGs had good diagnostic value in KD. qRT-PCR showed that WIPI1 and GBA were significantly upregulated.CONCLUSIONTwenty potential ARGs were identified by bioinformatics analysis, and WIPI1 and GBA may be used as potential drug targets and biomarkers.

2019-08-01·Journal of Biological Chemistry2区 · 生物学

The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases

2区 · 生物学

Article

作者: García-Torres, Desirée ; Fierke, Carol A

Ras family small GTPases undergo prenylation (such as farnesylation) for proper localization to the plasma membrane, where they can initiate oncogenic signaling pathways. Small GTP-binding protein GDP-dissociation stimulator (SmgGDS) proteins are chaperones that bind and traffic small GTPases, although their exact cellular function is unknown. Initially, SmgGDS proteins were classified as guanine nucleotide exchange factors, but recent findings suggest that SmgGDS proteins also regulate prenylation of small GTPases in vivo in a substrate-selective manner. SmgGDS-607 recognizes the polybasic region and the CAAX box of several small GTPases and inhibits prenylation by impeding their entry into the geranylgeranylation pathway. Here, using recombinant and purified enzymes for prenylation and protein-binding assays, we demonstrate that SmgGDS-607 differentially regulates farnesylation of several small GTPases. SmgGDS-607 inhibited farnesylation of some proteins, such as DiRas1, by sequestering the protein and limiting modification catalyzed by protein farnesyltransferase (FTase). We found that the competitive binding affinities of the small GTPase for SmgGDS-607 and FTase dictate the extent of this inhibition. Additionally, we discovered that SmgGDS-607 increases the rate of farnesylation of HRas by enhancing product release from FTase. Our work indicates that SmgGDS-607 binds to a broad range of small GTPases and does not require a PBR for recognition. Together, these results provide mechanistic insight into SmgGDS-607-mediated regulation of farnesylation of small GTPases and suggest that SmgGDS-607 has multiple modes of substrate recognition.