Last update 19 Sep 2024

SLC20A1

Last update 19 Sep 2024

Basic Info

Synonyms

gibbon ape leukemia virus receptor 1, Glvr-1, GLVR1

+ [8]

Introduction

Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:7929240, PubMed:8041748, PubMed:19726692, PubMed:17494632, PubMed:16790504). May play a role in extracellular matrix and cartilage calcification as well as in vascular calcification (PubMed:11009570). Essential for cell proliferation but this function is independent of its phosphate transporter activity (PubMed:19726692). (Microbial infection) May function as a retroviral receptor as it confers human cells susceptibility to infection to Gibbon Ape Leukemia Virus (GaLV), Simian sarcoma-associated virus (SSAV) and Feline leukemia virus subgroup B (FeLV-B) as well as 10A1 murine leukemia virus (10A1 MLV).

Drugs associated with SLC20A1

AP-306

Target

NaPi-2b x P-gp x SLC20A1 x SLC20A2

Mechanism

NaPi-2b inhibitors [+3]

Active Org.

Shanghai Alebund Pharmaceuticals Co., Ltd.

Originator Org.

Shanghai Alebund Pharmaceuticals Co., Ltd.

Active Indication

Chronic Kidney Diseases [+1]

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SLC20A1

CTR20230189 / CompletedPhase 2

一项在接受维持性血液透析的慢性肾脏病高磷血症患者中评价AP-306安全性和血清磷降低作用的II期、随机、开放、阳性药物对照、多中心研究

[Translation] A Phase II, randomized, open-label, active-controlled, multicenter study to evaluate the safety and serum phosphorus-lowering effect of AP-306 in patients with chronic kidney disease and hyperphosphatemia receiving maintenance hemodialysis

本研究的主要疗效目的是根据以下终点评价 AP-306 的有效性：在接受维持性血液透析的高磷血症患者中探索 AP-306 降低血清磷水平的能力；安全性目的是评价AP-306的总体安全性和耐受性。

[Translation]

The primary efficacy objective of this study is to evaluate the effectiveness of AP-306 based on the following endpoints: exploring the ability of AP-306 to reduce serum phosphorus levels in patients with hyperphosphatemia receiving maintenance hemodialysis; the safety objective is to evaluate the overall safety and tolerability of AP-306.

Start Date20 Feb 2023

Sponsor / Collaborator

Shanghai Alebund Pharmaceuticals Co., Ltd.

NCT05764590 / CompletedPhase 2

A Phase 2, Randomized, Open-Label, Active-Controlled, Multicenter Study to Evaluate the Safety and Serum Phosphorus Lowering Effect of AP-306 in Chronic Kidney Disease Patients Receiving Maintenance Hemodialysis With Hyperphosphatemia

The goal of this clinical trial is to learn about the following questions in the patients receiving maintenance hemodialysis with elevated blood phosphorus:
How much effect AP-306 has assessed by blood phosphorus lowering;
How safe and tolerable AP-306 is.
Participants will receive either following treatments:
AP-306, and
Sevelamer carbonate.

Start Date20 Feb 2023

Sponsor / Collaborator

Shanghai Alebund Pharmaceuticals Co., Ltd.

NCT02965053 / CompletedPhase 1

A Single-center, Randomized, 2-Period, Crossover, Study to Explore The Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of EOS789 in Patients With Chronic Kidney Disease and Hyperphosphatemia on Hemodialysis

This study is a randomized study designed as a 2x2 cross-over in two periods (Period 1 and Period 2) to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of EOS789 in patients with chronic kidney disease (CKD) and hyperphosphatemia receiving hemodialysis. Period 1 is double-blind and Period 2 is open-label. Period 1 and Period 2 are identical with regard to the design, inclusion/exclusion criteria, and assessments. EOS789 and its combination with sevelamer carbonate are tested in Period 1 and Period 2 respectively.

Start Date01 Dec 2016

Sponsor / Collaborator

Chugai Pharmaceutical Co., Ltd.

100 Clinical Results associated with SLC20A1

100 Translational Medicine associated with SLC20A1

0 Patents (Medical) associated with SLC20A1

171

Literatures (Medical) associated with SLC20A1

01 Jul 2024·Current Opinion in Nephrology & Hypertension

Phosphate sensing in health and disease

Review

Author: Rhee, Eugene P. ; Zechner, Christoph

Purpose of reviewDisruptions of phosphate homeostasis are associated with a multitude of diseases with insufficient treatments. Our knowledge regarding the mechanisms underlying metazoan phosphate homeostasis and sensing is limited. Here, we highlight four major advancements in this field during the last 12–18 months.Recent findingsFirst, kidney glycolysis senses filtered phosphate, which results in the release of glycerol 3-phosphate (G-3-P). Circulating G-3-P then stimulates synthesis of the phosphaturic hormone fibroblast growth factor 23 in bone. Second, the liver serves as a postprandial phosphate reservoir to limit serum phosphate excursions. It senses phosphate ingestion and triggers renal excretion of excess phosphate through a nerve-dependent mechanism. Third, phosphate-starvation in cells massively induces the phosphate transporters SLC20A1/PiT1 and SLC20A2/PiT2, implying direct involvement of cellular phosphate sensing. Under basal phosphate-replete conditions, PiT1 is produced but immediately destroyed, which suggests a novel mechanism for the regulation of PiT1 abundance. Fourth, Drosophila melanogaster intestinal cells contain novel organelles called PXo bodies that limit intracellular phosphate excursions. Phosphate starvation leads to PXo body dissolution, which triggers midgut proliferation.SummaryThese studies have opened novel avenues to dissect the mechanisms that govern metazoan phosphate sensing and homeostasis with the potential to identify urgently needed therapeutic targets.

23 May 2024·Journal of Biomolecular Structure and Dynamics

Computational analysis of sodium-dependent phosphate transporter SLC20A1/PiT1 gene identifies missense variations C573F, and T58A as high-risk deleterious SNPs

Article

Author: Santhy, K S ; Vineeth Kumar, T V ; Payva, Febby ; James, Remya ; Kanchi, Subbarao ; Siva Sankari, G ; Sivaramakrishnan, Venketesh

SLC20A1/PiT1 is a sodium-dependent inorganic phosphate transporter, initially recognized as the retroviral receptor for Gibbon Ape Leukemia Virus in humans. SNPs in SLC20A1 is associated with Combined Pituitary Hormone Deficiency and Sodium Lithium Counter transport. Using in silico techniques, we have screened the nsSNPs for their deleterious effect on the structure and function of SLC20A1. Screening with sequence and structure-based tools on 430 nsSNPs, filtered 17 nsSNPs which are deleterious. To evaluate the role of these SNPs, protein modeling and MD simulations were performed. A comparative analysis of model generated with SWISS-MODEL and AlphaFold shows that many residues are in the disallowed region of Ramachandran plot. Since SWISS-MODEL structure has a 25-residue deletion, the AlphaFold structure was used to perform MD simulation for equilibration and structure refinement. Further, to understand perturbation of energetics, we performed in silico mutagenesis and ΔΔG calculation using FoldX on MD refined structures, which yielded SNPs that are neutral (3), destabilizing (12) and stabilizing (2) on protein structure. Furthermore, to elucidate the impact of SNPs on structure, we performed MD simulations to discern the changes in RMSD, Rg, RMSF and LigPlot of interacting residues. RMSF profiles of representative SNPs revealed that A114V (neutral) and T58A (positive) were more flexible & C573F (negative) was more rigid compared to wild type, which is also reflected in the changes in number of local interacting residues in LigPlot and ΔΔG. Taken together, our results show that SNPs can lead to structural perturbations and impact the function of SLC20A1 with potential implications for disease.Communicated by Ramaswamy H. Sarma.

01 Apr 2024·Advanced Science

Inorganic Phosphate as “Bioenergetic Messenger” Triggers M2‐Type Macrophage Polarization

Article

Author: Li, Zhiyu ; Sun, Xiaoqing ; Wu, Yao ; He, Jing ; Wang, Xiang

AbstractThe effects of calcium phosphate (CaP) materials on macrophage polarization state vary with their physicochemical properties. The study aims to elucidate the impact of phosphate ion‐mediated energy metabolism on M2 macrophage polarization and the corresponding regulatory mechanism. The phosphate ions released from CaP ceramic as bioenergetic factor is identified; its concentration is closely associated with the polarized state. After being taken up by the sodium‐dependent phosphate transporter 1, extracellular phosphate ions produce energy via oxidative phosphorylation by facilitating tricarboxylic acid flux, thereby contributing to M2 macrophage polarization. Further mechanistic analysis reveals that the elevation of the bioenergetic basis can drive macrophage M2 polarization via the AMP‐activated protein kinase‐mammalian target of rapamycin (AMPK‐mTOR) axis. Another regulatory effect is that of the adenosine triphosphate (ATP), a signaling molecule. Intracellular ATP is released into the extracellular space and degraded to adenosine, which serves as a signaling molecule through the A2b adenosine receptor to activate the cyclic adenosine monophosphate (cAMP) pathway, thereby promoting M2 macrophage polarization. Overall, these findings may transform the existing knowledge on cell metabolism and energy homeostasis from bystanders to pivotal factors guiding M2 macrophage polarization and have implications for the future design of biomimetic CaP scaffolds.

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SLC20A1

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