更新于：2024-11-01

PROT

更新于：2024-11-01

基本信息

别名

brain-specific L-proline transporter、PROT、SLC6A7

+ [4]

简介

Brain specific sodium (and chloride)-dependent proline transporter (PubMed:7651355). Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals (Probable).

关联

项与 PROT 相关的药物

LQFM215

靶点

PROT

作用机制

PROT抑制剂

在研机构

Universidade Federal de Goiás

原研机构

Universidade Federal de Goiás

在研适应症

精神分裂症

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

LX-6171

靶点

PROT

作用机制

PROT抑制剂

在研机构-

原研机构

Lexicon Pharmaceuticals, Inc.

在研适应症-

非在研适应症

记忆障碍

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 PROT 相关的临床试验

NCT00691808 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Study to Determine Safety and Tolerability of LX6171 Oral Suspension Dosed for 28 Days in Subjects Exhibiting Age Associated Memory Impairment (AAMI)

The purpose of the study is to determine the safety, tolerability, and effectiveness of 2 dose levels of LX6171 given over 28 days in patients with Age Associated Memory Impairment (AAMI).

开始日期2008-02-01

申办/合作机构

Lexicon Pharmaceuticals, Inc.

EUCTR2007-005241-38-NL / Not yet recruitingN/A

A Randomized, Double-Blind, Placebo-Controlled Study to Determine Safety and Tolerability of LX6171 Oral Suspension Dosed for 28 Days in Subjects Exhibiting Age Associated Memory Impairment (AAMI) with a Lead-in, Open-Label, Single-Dose Relative Bioavailability Study of LX6171 Oral Suspension in Healthy Elderly Subjects

开始日期2007-11-12

申办/合作机构

Lexicon Pharmaceuticals, Inc.

100 项与 PROT 相关的临床结果

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100 项与 PROT 相关的转化医学

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0 项与 PROT 相关的专利（医药）

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116

项与 PROT 相关的文献（医药）

2024-09-01·Journal of Pharmacy and Pharmacology

In silico evidence of bitopertin’s broad interactions within the SLC6 transporter family

Article

作者: Chiareli, Raphaela Almeida ; Gomez, Renato Santiago ; Junior, Guilhermino Pereira Nunes ; Nascimento, Lucas Rodrigues Couto ; Campos, Bruna Kelly Pedrosa ; de Carvalho, Gustavo Almeida ; Menegatti, Ricardo ; Pinto, Mauro Cunha Xavier ; Tambwe, Paul Magogo

AbstractThe Glycine Transporter Type 1 (GlyT1) significantly impacts central nervous system functions, influencing glycinergic and glutamatergic neurotransmission. Bitopertin, the first GlyT1 inhibitor in clinical trials, was developed for schizophrenia treatment but showed limited efficacy. Despite this, bitopertin’s repositioning could advance treating various pathologies. This study aims to understand bitopertin’s mechanism of action using computational methods, exploring off-target effects, and providing a comprehensive pharmacological profile. Similarity Ensemble Approach (SEA) and SwissTargetPrediction initially predicted targets, followed by molecular modeling on SWISS-MODEL and GalaxyWeb servers. Binding sites were identified using PrankWeb, and molecular docking was performed with DockThor and GOLD software. Molecular dynamics analyses were conducted on the Visual Dynamics platform. Reverse screening on SEA and SwissTargetPrediction identified GlyT1 (SLC6A9), GlyT2 (SLC6A5), PROT (SLC6A7), and DAT (SLC6A3) as potential bitopertin targets. Homology modeling on SwissModel generated high-resolution models, optimized further on GalaxyWeb. PrankWeb identified similar binding sites in GlyT1, GlyT2, PROT, and DAT, indicating potential interaction. Docking studies suggested bitopertin’s interaction with GlyT1 and proximity to GlyT2 and PROT. Molecular dynamics confirmed docking results, highlighting bitopertin’s target stability beyond GlyT1. The study concludes that bitopertin potentially interacts with multiple SLC6 family targets, indicating a broader pharmacological property.

2024-07-01·Science of The Total Environment

Physiological and transcriptomic analysis provides new insights into osmoregulation mechanism of Ruditapes philippinarum under low and high salinity stress

Article

作者: Ding, Jianfeng ; Nie, Hongtao ; Huo, Zhongming ; Liu, Tao ; Yan, Xiwu

The Manila clam (Ruditapes philippinarum) is a commercially important marine bivalve, which inhabits the estuarine and mudflat areas. The osmoregulation is of great significance for molluscs adaptation to salinity fluctuations. In this study, we investigated the effects of low salinity (10 psu) and high salinity (40 psu) stress on survival and osmoregulation of the R. philippinarum. The results of physiological parameters showed that the ion (Na⁺, K⁺, Cl^-) concentrations and Na⁺/K⁺-ATPase (NKA) activity of R. philippinarum decreased significantly under low salinity stress, but increased significantly under high salinity stress, indicating that there are differences in physiological adaptation of osmoregulation of R. philippinarum. In addition, we conducted the transcriptome analysis in the gills of R. philippinarum exposed to low (10 psu) and high (40 psu) salinity challenge for 48 h using RNA-seq technology. A total of 153 and 640 differentially expressed genes (DEGs) were identified in the low salinity (LS) group and high salinity (HS) group, respectively. The immune (IAP, TLR6, C1QL4, Ank3), ion transport (Slc34a2, SLC39A14), energy metabolism (PCK1, LDLRA, ACOX1) and DNA damage repair-related genes (Gadd45g, HSP70B2, GATA4) as well as FoxO, protein processing in endoplasmic reticulum and endocytosis pathways were involved in osmoregulation under low salinity stress of R. philippinarum. Conversely, the ion transport (SLC6A7, SLC6A9, SLC6A14, TRPM2), amino acid metabolism (GS, TauD, ABAT, ALDH4A1) and immune-related genes (MAP2K6, BIRC7A, CTSK, GVIN1), and amino acid metabolism pathways (beta-Alanine, Alanine, aspartate and glutamate, Glutathione) were involved in the process of osmoregulation under high salinity stress. The results obtained here revealed the difference of osmoregulation mechanism of R. philippinarum under low and high salinity stress through physiological and molecular levels. This study contributes to the assessment of salinity adaptation of bivalves in the context of climate change and provides useful information for marine resource conservation and aquaculture.

2024-01-01·iScience

Prothymosin α accelerates dengue virus-induced thrombocytopenia

Article

作者: Liu, Kuan-Ting ; Su, Bing-Hua ; Shiau, Ai-Li ; Chen, Yi-Cheng ; Lin, Chia-Ling ; Yang, Mei-Lin ; Chen, Yen-Hsu ; Wu, Chao-Liang ; Lu, I-An

Thrombocytopenia is the hallmark finding in dengue virus (DENV) infection. Prothymosin α (ProT) has both intracellular and extracellular functions involved in cell cycle progression, cell differentiation, gene regulation, oxidative stress response, and immunomodulation. In this study, we found that ProT levels were elevated in dengue patient sera as well as DENV-infected megakaryoblasts and their culture supernatants. ProT transgenic mice had reduced platelet counts with prolonged bleeding times. Upon treatment with DENV plus anti-CD41 antibody, they exhibited severe skin hemorrhage. Furthermore, overexpression of ProT suppressed megakaryocyte differentiation. Infection with DENV inhibited miR-126 expression, upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1), downregulated GATA-1, and increased ProT expression. Upregulation of ProT led to Nrf2 activation and reduced reactive oxygen species production, thereby suppressing megakaryopoiesis. We report the pathophysiological role of ProT in DENV infection and propose an involvement of the miR-126-DNMT1-GATA-1-ProT-Nrf2 signaling axis in DENV-induced thrombocytopenia.