预约演示

更新于：2025-05-07

SLC20A1

更新于：2025-05-07

基本信息

别名

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

+ [8]

简介

Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion (PubMed:11009570, PubMed:16790504, PubMed:17494632, PubMed:19726692, PubMed:7929240, PubMed:8041748). 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).

关联

项与 SLC20A1 相关的药物

AP-306

靶点

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

作用机制

NaPi-2b抑制剂 [+3]

在研机构

上海礼邦医药科技有限公司

原研机构

上海礼邦医药科技有限公司

在研适应症

慢性肾病 [+1]

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

项与 SLC20A1 相关的临床试验

NCT06712654

/ Not yet recruiting临床2期

A Phase 2b, Randomized, Double-Blinded, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Serum Phosphate Lowering Effect of Fixed Dosed AP306 in Patients Receiving Maintenance Hemodialysis with Hyperphosphatemia

The goal of this clinical trial is to learn if AP306 could work in the patients receiving maintenance hemodialysis with elevated blood phosphate. The main questions it aims to answer are:
* Does AP306 lower blood phosphate levels when the participants take a fixed dose of AP306?
* What medical problems do the participants have when taking AP306?
The researchers will compare AP306 to a placebo (a look-alike substance that contains no drug) to see if AP306 works to treat hyperphosphatemia.
The participants will:
* Stop all using blood phosphate-lowering drugs, and
* Take AP306 or a placebo three times a day for 12 weeks.
If the participant has a blood phosphate level above a certain level, they will receive additional treatment to lower the blood phosphate level.

开始日期2025-04-10

申办/合作机构

上海礼邦医药科技有限公司

CTR20230189

/ Completed临床2期

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

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。

开始日期2023-02-20

申办/合作机构

上海礼邦医药科技有限公司

NCT05764590

/ Completed临床2期

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.

开始日期2023-02-20

申办/合作机构

上海礼邦医药科技有限公司

100 项与 SLC20A1 相关的临床结果

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100 项与 SLC20A1 相关的转化医学

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0 项与 SLC20A1 相关的专利（医药）

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154

项与 SLC20A1 相关的文献（医药）

2025-05-01·Experimental Cell Research

Type III sodium-dependent inorganic phosphate transporters are required for the phenotypes in human brain microvascular endothelial cells

Article

作者: Murata, Junya ; Ohuchi, Kazuki ; Izutsu, Mutsuko ; Inden, Masatoshi ; Mishima, Ayane ; Hayashi, Yuichi ; Kurita, Hisaka ; Watanabe, Ku ; Hozumi, Isao

Inorganic phosphate (Pi) homeostasis in the brain is critical for the development of primary brain calcification (PBC). In the brains of patients with PBC, calcification occurs in the cerebral small vessels, and it is primarily caused by mutated SLC20A2, a gene that encodes a type III Pi transporter. A previous study founded that the SLC20 family, which includes SLC20A1 and SLC20A2, contributes to Pi homeostasis in the central nervous system. However, the impact of these Pi transporters on the brain vessel phenotype remains unknown. Thus, in this study, we aimed to investigate the effect of SLC20A1 or SLC20A2 depletion on the phenotype of human brain microvascular endothelial cells (hBMECs). We assessed the primary phenotypes of vascular endothelial cells, such as proliferation, tube formation, and VE-cadherin expression. The results showed that hBMECs silenced for SLC20A1 or SLC20A2 had decreased proliferative and angiogenic ability, as well as VE-cadherin expression. The intracellular Pi concentration ([Pi]_i) remained constant in SLC20A1-silenced hBMECs whereas it increased in SLC20A2-silenced cells. Tube formation ability was no change even at 3 mM, a concentration higher than [Pi]_i which was increased in SLC20A2-silenced hBMECs. Thus, increased [Pi]_i in SLC20A2-silenced hBMECs may have a small impact on phenotypic changes. In conclusion, abnormalities in Pi homeostasis caused by SLC20A2 depletion were suggested to play a minor role in PBC endothelial pathology.

2024-10-22·Journal of Virology

Sodium-dependent phosphate transporter PiT1/SLC20A1 as the receptor for the endogenous retroviral envelope syncytin-B involved in mouse placenta formation

Article

作者: Bireau, Caroline ; Pierron, Gérard ; Heidmann, Thierry ; Souquere, Sylvie ; Préault, Noémie ; Dupressoir, Anne ; Cassonnet, Patricia ; Jacob, Yves ; Bacquin, Agathe ; Beck, Laurent ; Mousseau, Guillaume

ABSTRACTSyncytins are envelope genes of retroviral origin that play a critical role in the formation of a syncytial structure at the fetomaternal interface via their fusogenic activity. The mouse placenta is unique among placental mammals since the fetomaternal interface comprises two syncytiotrophoblast layers (ST-I and ST-II) instead of one observed in all other hemochorial placentae. Each layer specifically expresses a distinct mouse syncytin, namely syncytin-A (SynA) for ST-I and syncytin-B (SynB) for ST-II, which have been shown to be essential to placentogenesis and embryonic development. The cellular receptor for SynA has been identified as the membrane protein LY6E and is not the receptor for SynB. Here, by combining a cell–cell fusion assay with the screening of a human ORFeome-derived expression library, we identified the transmembrane multipass sodium-dependent phosphate transporter 1 PiT1/SLC20A1 as the receptor for SynB. Transfection of cells with the cloned receptor, but not the closely related PiT2/SLC20A2, leads to their fusion with cells expressing SynB, with no cross-reactive fusion activity with SynA. The interaction between the two partners was further demonstrated by immunoprecipitation. PiT1/PiT2 chimera and truncation experiments identified the PiT1 N-terminus as the major determinant for SynB-mediated fusion. RT-qPCR analysis of PiT1 expression on a panel of mouse adult and fetal tissues revealed a concomitant increase of PiT1 and SynB specifically in the developing placenta. Finally, electron microscopy analysis of the placenta of PiT1 null embryo before they die (E11.5) disclosed default of ST-II formation with lack of syncytialization, as previously observed in cognate SynB null placenta, and consistent with the present identification of PiT1 as the SynB partner. IMPORTANCE Syncytins are envelope genes of endogenous retroviruses, coopted for a physiological function in placentation. They are fusogenic proteins that mediate cell–cell fusion by interacting with receptors present on the partner cells. Here, by devising an in vitro fusion assay that enables the screening of an ORFeome-derived expression library, we identified the long-sought receptor for syncytin-B (SynB), a mouse syncytin responsible for syncytiotrophoblast formation at the fetomaternal interface of the mouse placenta. This protein – PiT1/SLC20A1 – is a multipass transmembrane protein, also known as the receptor for a series of infectious retroviruses. Its profile of expression is consistent with a role in both ancestral endogenization of a SynB founder retrovirus and present-day mouse placenta formation, with evidence—in PiT1 knockout mice—of unfused cells at the level of the cognate placental syncytiotrophoblast layer.

2024-10-01·The American Journal of Dermatopathology

Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm

Article

作者: Cho, Woo Cheal ; Prieto, Victor G ; Yang, Richard K

Abstract:Spitz melanocytic neoplasms exhibit frequent chromosomal rearrangements leading to recurring gene fusions, such as ALK fusions. TPM3 and DCTN1 emerge as the predominant fusion partners of ALK, although less common partners such as NPM1, TPR, CLIP1, GTF3C2, MLPH, EEF2, MYO5A, and KANK1 have also been documented. Although ALK fusions are primarily associated with Spitz nevi or atypical Spitz tumors, instances of Spitz melanoma with ALK fusions documented in the English literature are exceedingly rare. Here, we present a case of Spitz melanoma harboring SLC20A1::ALK fusion, highlighting a novel fusion transcript not previously reported in Spitz melanocytic neoplasms, including Spitz melanomas. In addition, the tumor exhibits multiple aberrant chromosomal alterations characteristic of melanoma, along with a somatic mutation in GRM3.

项与 SLC20A1 相关的新闻（医药）

2024-06-17

·医药观澜

礼邦医药小分子新药拟纳入突破性治疗品种

▎药明康德内容团队编辑今日（6月17日），中国国家药监局药品审评中心（CDE）官网公示，礼邦医药的AP306胶囊拟纳入突破性治疗品种，拟开发的适应症为慢性肾脏病高磷血症。根据礼邦医药公开资料，AP306是一种钠依赖性磷酸盐转运蛋白泛抑制剂，已完成针对慢性肾脏病高磷血症的2期临床研究。截图来源：CDE官网高磷血症是慢性肾脏病患者的最常见的并发症之一。血磷水平长期升高可导致甲状旁腺功能亢进、肾性骨病、血管钙化等多种并发症，是患者心血管事件和全因死亡的独立危险因素。控制血磷水平达标可有效改善慢性肾脏病患者预后。对于接受透析治疗的慢性肾脏病患者，即使规律透析也无法清除体内蓄积的磷酸盐。由于低磷饮食导致营养不良的限制，口服磷酸盐结合剂是目前高磷血症的主要治疗方法，但对于许多患者，通过现有的治疗选择仍不能使血磷得到有效控制。根据礼邦医药公开资料，AP306（EOS789）是一种口服磷酸盐转运蛋白NaPi-IIb、PiT-1、PiT-2泛抑制剂，能阻断肠道磷酸盐主动转运，有望克服低磷饮食和磷结合剂治疗高磷血症的局限性。该药最初由日本中外制药（Chugai Pharmaceutical）发现。目前，礼邦医药已全面行使选择权，独家拥有AP306的全球开发和商业化权利。在今年5月举行的第61届欧洲肾脏协会（ERA）年会上，礼邦医药以专题口头报告形式公布了AP306在血液透析合并高磷血症患者中的2期临床研究数据，该研究在中国 11家研究中心完成。在该2期临床试验中，55例血液透析合并高磷血症患者随机接受AP306（N=27）和碳酸司维拉姆（N=28）治疗12周。每4周调整一次AP306和碳酸司维拉姆的剂量，以保持血清磷控制在3.5–5.5 mg/dL的目标范围。AP306的试验剂量从每次75 mg、一日三次开始，随餐服用，逐步增加到每次125 mg和150 mg、一日三次。在两组在主要疗效终点，即从基线到治疗结束时血清磷平均值的变化方面，两组均达到有统计学意义的下降，其中AP306组为-2.51 mg/dL，其血清磷下降幅度明显高于碳酸司维拉姆组（-1.08 mg/dL）。在治疗期间，AP306组血清磷平均值随治疗的延长而逐渐降低，从第3周末开始低于碳酸司维拉姆组并持续至治疗结束。虽然达到研究定义的血清磷目标范围（3.5– 5.5 mg/dL）的患者比例在两组之间相当，但AP306组达到KDIGO推荐的血清磷目标范围（2.5 – 4.5 mg/dL）的患者比例明显高于碳酸司维拉姆组。在治疗的最后4周，AP306组的平均每日剂量（288.30 mg/天）低于碳酸司维拉姆组（4650.99 mg/天）。 AP306组最常见的不良事件为胃肠道反应，主要是腹泻。所有腹泻事件严重程度均为1/2级且大多数在2周内自行缓解。AP306组未报告严重不良事件。参考资料：[1]中国药物临床试验登记与信息公示平台. Retrieved June 17，2024, From https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d[2]礼邦医药在第 61 届欧洲肾脏协会（ERA）年会上公布其 AP306 Ⅱ期临床试验数据. Retrieved Mar 27 , 2024, from https://mp.weixin.qq.com/s/2ZgA8pfwiNHCeQTY0zam5w 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

突破性疗法临床2期