更新于：2024-05-01

SLC7A5

L-型氨基酸转运蛋白-1

更新于：2024-05-01

基本信息

别名

大分子中性氨基酸转运子1、4F2 LC、4F2 light chain

+ [16]

简介

The heterodimer with SLC3A2 functions as sodium-independent, high-affinity transporter that mediates uptake of large neutral amino acids such as phenylalanine, tyrosine, leucine, histidine, methionine, tryptophan, valine, isoleucine and alanine (PubMed:9751058, PubMed:10049700, PubMed:11557028, PubMed:10574970, PubMed:11564694, PubMed:12117417, PubMed:12225859, PubMed:25998567, PubMed:30867591, PubMed:18262359, PubMed:15769744). The heterodimer with SLC3A2 mediates the uptake of L-DOPA (By similarity). Functions as an amino acid exchanger (PubMed:11557028, PubMed:12117417, PubMed:12225859, PubMed:30867591). May play a role in the transport of L-DOPA across the blood-brain barrier (By similarity). May act as the major transporter of tyrosine in fibroblasts (Probable). May mediate blood-to-retina L-leucine transport across the inner blood-retinal barrier (By similarity).Can mediate the transport of thyroid hormones diiodothyronine (T2), triiodothyronine (T3) and thyroxine (T4) across the cell membrane (PubMed:11564694). When associated with LAPTM4B, the heterodimer formed by SLC3A2 and SLC7A5 is recruited to lysosomes to promote leucine uptake into these organelles, and thereby mediates mTORC1 activation (PubMed:25998567). Involved in the uptake of toxic methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes (PubMed:12117417). Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the membrane (PubMed:15769744). (Microbial infection) In case of hepatitis C virus/HCV infection, the complex formed by SLC3A2 and SLC7A5/LAT1 plays a role in HCV propagation by facilitating viral entry into host cell and increasing L-leucine uptake-mediated mTORC1 signaling activation, thereby contributing to HCV-mediated pathogenesis.

关联

项与 SLC7A5 相关的药物

TX-101

碘[131I]-IPA

靶点

SLC7A5

作用机制

SLC7A5抑制剂

在研机构

Telix International Pty Ltd [+1]

原研机构

Telix Pharmaceuticals Ltd.

在研适应症

多形性胶质母细胞瘤 [+2]

非在研适应症-

最高研发阶段临床3期

首次获批国家/地区-

首次获批日期1800-01-20

OKY-034

靶点

SLC7A5

作用机制

SLC7A5抑制剂

在研机构

KNC Laboratories Co., Ltd. [+2]

原研机构

Osaka University [+1]

在研适应症

胰腺癌 [+1]

非在研适应症-

最高研发阶段临床2/3期

首次获批国家/地区-

首次获批日期1800-01-20

R-OKY-034F

靶点

SLC7A5

作用机制

SLC7A5抑制剂

在研机构

Japan Agency For Medical Research And Development [+1]

原研机构

Osaka University

在研适应症

胰腺癌

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 SLC7A5 相关的临床试验

NCT05632562 / Not yet recruiting早期临床1期IIT

Multiparametic Metabolic and Hypoxic PET/MRI for Disease Assessment in High Grade Glioma

This feasibility study will assess the clinical potential of a new imaging approach to detect viable high grade glioma (HGG) in pediatric and adult patients after standard of care radiation therapy (RT) with or without concurrent temozolomide (TMZ). Study participants will undergo simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with O-([2-[F-18]fluoroethyl)-L-tyrosine (FET, amino acid transport) and 1H-1-(3-[F-18]fluoro-2-hydroxypropyl)-2-nitroimidazole (FMISO, hypoxia) at the time of standard of care imaging after completion of RT. The presence of viable tumor at this time point will be assessed on a per patient basis. Study participants will be followed clinically and with standard of care (SOC) imaging for up to 2 years after completion of PET/MRI to determine the nature of lesions seen on investigational imaging and to obtain patient outcome data. The imaging data will also be used to develop a semi-automated workflow suitable for implementation in clinical trials and standard of care PET/MRI studies.

开始日期2025-06-01

申办/合作机构

The University of Alabama at Birmingham

NCT06388863 / Not yet recruitingN/AIIT

Evaluation of the Efficacy and Safety of Fecal Microbiota Transplantation for Parkinson's Disease Patients With Constipation

Participants will be allocated to FMT group or placebo group at a 1:1 ratio. For interventional group, patients will be given six FMT capsules twice a week for 24 weeks. Placebo capsules are identical in appearance and smell but contain milk powder. During visitpoints, participants complete specific scales to assess improvement in constipation, emotion and quality of life. Besides, fecal samples are collected for metagenomics and metabolomics sequencing and blood samples are tested peripheral concentration of levodopa.

开始日期2024-06-01

申办/合作机构

复旦大学附属中山医院

NCT05450744 / Recruiting临床1期

A Phase 1 Safety and Dose Finding Study of 131I -TLX101 Plus Standard of Care in Patients With Newly Diagnosed Glioblastoma

This is an open label, single arm, parallel-group, multicentre, and dose finding study to evaluate the safety of ascending radioactive dose levels of 131I-TLX101 administered intravenously in combination with best standard of care in newly diagnosed GBM patients.

开始日期2023-04-01

申办/合作机构

Telix International Pty Ltd

100 项与 SLC7A5 相关的临床结果

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100 项与 SLC7A5 相关的转化医学

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0 项与 SLC7A5 相关的专利（医药）

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1,055

项与 SLC7A5 相关的文献（医药）

2024-03-01·European journal of obstetrics & gynecology and reproductive biology: X

Evaluation of amniotic fluid neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein levels during pregnancy.

Article

作者: Daisuke Katsura ; Shunichiro Tsuji ; Shinsuke Tokoro ; Ayako Inatomi ; Takako Hoshiyama ; Nobuyuki Kita ; Takashi Murakami

Objective:

We aimed to examine amniotic fluid neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) levels during pregnancy.

Study design:

This study included singleton pregnancies. Amniotic fluid samples were collected at the time of vaginal delivery, cesarean section, amniocentesis, amnioreduction, and amnioinfusion. We analyzed changes of the NGAL and L-FABP levels during pregnancy and the factors affecting these values and their association with clinical outcomes.

Results:

Three hundred and one pregnancies were analyzed. Respective Pearson correlation coefficients for the NGAL and L-FABP levels and gestational age at inspection were - 0.351 and - 0.819 (p <0.001 and p < 0.001, respectively); weak and strong negative correlation were observed. The NGAL level was significantly higher in the intra-amniotic infection group than in the control group (p < 0.001). The L-FABP level was significantly higher in the fetal blood flow abnormalities group than in the control group (p < 0.001). The NGAL and L-FABP levels were significantly higher in the adverse outcomes group than in the control group (p = 0.019 and p < 0.001, respectively), and the respective areas under the concentration-time curve, with optimal cutoff values, for the NGAL and L-FABP levels were 0.693 (14,800 µg/gCr) and 0.864 (378 µg/gCr).

Conclusions:

Amniotic fluid NGAL and L-FABP levels reflect fetal and neonatal immaturity. Additionally, the NGAL level is a useful predictive factor of intra-amniotic infection, and the L-FABP level is a useful predictive factor of fetal condition and short- and long-term prognoses.

2024-03-01·Journal of pharmacological sciences

Inhibition of amino acid transporter LAT1 in cancer cells suppresses G0/G1-S transition by downregulating cyclin D1 via p38 MAPK activation

Article

作者: Zhou, Xinyu ; Ohgaki, Ryuichi ; Jin, Chunhuan ; Xu, Minhui ; Okanishi, Hiroki ; Endou, Hitoshi ; Kanai, Yoshikatsu

L-type amino acid transporter 1 (LAT1, SLC7A5) is upregulated in various cancers and associated with disease progression. Nanvuranlat (Nanv; JPH203, KYT-0353), a selective LAT1 inhibitor, suppresses the uptake of large neutral amino acids required for rapid growth and proliferation of cancer cells. Previous studies have suggested that the inhibition of LAT1 by Nanv induces the cell cycle arrest at G0/G1 phase, although the underlying mechanisms remain unclear. Using pancreatic cancer cells arrested at the restriction check point (R) by serum deprivation, we found that the Nanv drastically suppresses the G0/G1-S transition after release. This blockade of the cell cycle progression was accompanied by a sustained activation of p38 mitogen-activated protein kinase (MAPK) and subsequent phosphorylation-dependent proteasomal degradation of cyclin D1. Isoform-specific knockdown of p38 MAPK revealed the predominant contribution of p38α. Proteasome inhibitors restored the cyclin D1 amount and released the cell cycle arrest caused by Nanv. The increased phosphorylation of p38 MAPK and the decrease of cyclin D1 were recapitulated in xenograft tumor models treated with Nanv. This study contributes to delineating the pharmacological activities of LAT1 inhibitors as anti-cancer agents and provides significant insights into the molecular basis of the amino acid-dependent cell cycle checkpoint at G0/G1 phase.

2024-02-24·Cell death discovery

ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion.

Article

作者: Qingbo Meng ; Yuting Xie ; Kang Sun ; Lihong He ; Hongkun Wu ; Qi Zhang ; Tingbo Liang

Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m⁵C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m⁵C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8⁺ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m⁵C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8⁺ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m⁵C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.

项与 SLC7A5 相关的新闻（医药）

2024-04-04

·PRNewswire

Huahui Health to Present Preclinical Data of HH018-sesutecan at the 2024 AACR Annual Meeting

BEIJING, April 4, 2024 /PRNewswire/ -- Huahui Health Ltd.("Huahui Health"), a clinical stage biotechnology company focused on discovering and developing virology, hepatology, and oncology therapies, announced that it will present the results of preclinical data of HH018-sesutecan, a tumor microenvironment targeting CD98-directed ADC, at the American Association for Cancer Research (AACR) Annual Meeting 2024. The AACR meeting will be held April 5–10, 2024, in San Diego, California. Topic: A tumor microenvironment-targeting CD98-directed ADC confers robust anti-tumor activity in multiple cancers with favorable pharmacokinetics and safety profiles in preclinical models Session Title: Late-Breaking Research: Experimental and Molecular Therapeutics 4 Session Date and Time: Wednesday Apr 10, 2024 9:00 AM - 12:30 PM Location: Poster Section 54 Poster Board Number: 1 Abstract Presentation Number: LB425 Presenter: Bin Chen, CEO of Huahui Health. Zhu Chen, CSO of ProfoundBio About Huahui Health Huahui Health is a clinical-stage biotechnology company founded in 2015 in Beijing, China. With a focus on virology, hepatology, and oncology, the company is dedicated to drug discovery, development, and antibody engineering. It has expanded its pipeline to include promising drug candidates in virology and oncology, aiming to launch multiple groundbreaking products and lead the way in antiviral and oncology research. Two leading programs have entered the pivotal clinical trial stage. One is HH-003, the first anti-preS1 HBV/HDV neutralizing antibody to enter a pivotal study for chronic HDV infection. The other is HH-120, an IgM-like ACE2-Fc recombinant fusion protein via nasal spray, currently undergoing a phase 3 trial for post-exposure prophylaxis of SARS-CoV-2. For more information, please visit . SOURCE Huahui Health Ltd.

临床3期AACR会议

2024-04-04

·BioSpace

ProfoundBio to Present Data on Multiple Preclinical Programs From Its Antibody-Drug Conjugate Pipeline at the American Association for Cancer Research Annual Meeting 2024

SEATTLE, April 4, 2024 /PRNewswire/ --ProfoundBio, a clinical-stage biotechnology company dedicated to developing novel antibody-drug conjugate (ADC) therapies for patients with cancer, today announced its participation at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2024, taking place from April 5-10 in San Diego, California. ProfoundBio will showcase its innovative ADC programs through an oral presentation on its EGFR- and cMET-dual targeting ADC PRO1286, a poster presentation detailing preclinical data of a SLITRK6-directed ADC PRO1106, and a late-breaking poster presentation on a CD98-directed ADC developed in partnership with Huahui Health, a clinical-stage biotechnology company. "We are pleased to share our latest research at the AACR Meeting this year," stated Zhu Chen, Ph.D., Chief Scientific Officer of ProfoundBio. "These presentations underscore our commitment to leveraging our proprietary ADC platforms to target some of the most challenging cancers. With PRO1286, PRO1106, and our CD98-directed ADC, we are aiming to provide patients with more effective and tolerable treatment options, and look forward to sharing the latest findings with the scientific community." Key Presentations at AACR 2024 About ProfoundBio's ADC Programs FRα-Targeted ADC: Rinatabart sesutecan (Rina-S, PRO1184) Rina-S is a FRα-targeted ADC being developed as a novel treatment option for patients with ovarian and endometrial cancer, and other FRα-expressing cancers. Rina-S is comprised of a FRα-directed antibody conjugated to sesutecan, ProfoundBio's novel, proprietary hydrophilic exatecan-based linker-drug, at a homogeneous drug-to-antibody ratio (DAR) of 8. Exatecan is a potent, membrane permeable topoisomerase-1 inhibitor with strong bystander effect. The linker component of sesutecan is a highly hydrophilic, stable, cleavable linker designed to mask the hydrophobicity of exatecan, enabling high DAR and efficient delivery of the exatecan payload to tumors while maintaining favorable physicochemical and pharmacokinetic properties of the ADC. Rina-S is currently being evaluated in a Phase 1/2 clinical trial (NCT05579366) and has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of patients with FRα-expressing high-grade serous or endometrioid platinum-resistant ovarian cancer. CD70-Targeted ADC: PRO1160 PRO1160 is an ADC consisting of a CD70-targeted antibody conjugated to ProfoundBio's novel, proprietary hydrophilic exatecan-based linker-drug, sesutecan. CD70 is a protein expressed on both solid tumors and hematological malignancies including renal cell carcinoma, nasopharyngeal carcinoma, and non-Hodgkin lymphoma, yet is largely absent in normal tissues. With preclinical results showcasing encouraging pharmacokinetics, efficacy, and tolerability, PRO1160 is emerging as a potential advancement in the treatment of these cancers and is currently being evaluated in a Phase 1/2 clinical trial (NCT05721222). PTK7-Targeted ADC: PRO1107 PRO1107 is an ADC consisting of a PTK7-targeted antibody conjugated to ProfoundBio's novel, proprietary hydrophilic MMAE-based linker-drug, LD343, at a homogeneous DAR of 8. MMAE is a potent, membrane-permeable microtubule inhibitor that has been clinically validated as an ADC payload with multiple marketed vedotin ADCs at a DAR of 4. The linker component of LD343 is a highly hydrophilic, stable, cleavable linker designed to mask the hydrophobicity of MMAE, enabling high DAR and efficient delivery of the MMAE payload to tumors while maintaining favorable physicochemical and pharmacokinetic properties of the ADC. PRO1107 is currently being evaluated in a Phase 1/2 clinical trial (NCT06171789). Bispecific ADC: PRO1286 PRO1286 is a novel EGFR- and cMET-dual targeting ADC that has the potential to treat a broad range of tumors. PRO1286 is built on the clinically validated sesutecan platform and is anticipated to enter the clinic in 2024. About ProfoundBio ProfoundBio is a clinical-stage biotechnology company focused on the development of novel antibody-based therapeutics for patients with cancer. Built on internally developed, innovative, and proprietary technology platforms, ProfoundBio has developed a pipeline consisting of multiple ADC drug candidates targeting solid tumors and hematological malignancies. The company's disclosed development pipeline consists of rinatabart sesutecan (Rina-S; PRO1184), an ADC targeting FRα; PRO1160, an ADC targeting CD70; PRO1107, an ADC targeting PTK7; and PRO1286, a bispecific ADC targeting EGFR and cMET. ProfoundBio is headquartered in Seattle, Washington with an R&D center of innovation in Suzhou, China. For more information, please visit and follow us on LinkedIn. Investor Contact: ir@profoundbio.com Media Contact: Priyanka Shah 908-447-6134 pshah@elephantheadcommunicationsllc.com

快速通道抗体药物偶联物AACR会议

2024-02-25

·精准药物

浙江大学梁廷波团队：发现“癌中之王”胰腺癌最新靶点

本文为转化医学网原创，转载请注明出处作者：Rainbow导读：胰腺导管腺癌（PDAC）是一种由于血管发育不良和结缔组织增生而缺乏营养的肿瘤。2月24日，浙江大学梁廷波团队在期刊《Cell Death Discovery》上在线发表题为“ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion”的研究论文，研究阐明了ALYREF的临床意义及其在人类PDAC中的致癌作用。ALYREF敲低通过损害JunD-SLC7A5-mTORC1轴抑制PDAC细胞增殖并减弱肿瘤免疫逃逸。这些发现为开发PDAC的潜在治疗策略提供了新的见解。https://www.nature.com/articles/s41420-024-01862-2研究背景 01 胰腺导管腺癌（PDAC）是最致命的疾病之一，只有10-15%的患者适合接受手术切除。与其他类型的癌症相比，PDAC相对化疗耐药，并且存活益处非常有限。此外，靶向治疗和免疫检查点抑制剂在PDAC治疗中的作用有限。因此，迫切需要探索PDAC新的分子和生物机制，以确定有效的治疗策略和诊断生物标志物。高通量测序技术的快速发展揭示了一种新兴的基因调控机制，即表观转录组。表观转录组调控着编码RNA和非编码RNA的转录后修饰。迄今为止，已经发现了超过170种不同类型的影响RNA功能和稳态的RNA修饰。此外，越来越多证据表明，表观转录组失调在肿瘤发生中起着重要作用。最近的几项研究表明，m5C修饰的mRNA与肿瘤发生和进展有关。然而，m5C在PDAC中的作用仍然不清楚，需要进一步研究。癌细胞的代谢变化满足了细胞增殖和在营养限制条件下生存所诱导的生物合成需求。代谢重编程在许多类型的癌症中普遍观察到，被认为是肿瘤的一个重要特征。除了作为蛋白质的底物外，氨基酸还参与能量供应、氧化还原平衡和核苷酸合成。为了满足指数生长和增殖的需求，肿瘤细胞经常过表达与氨基酸相关的一些酶或转运蛋白。充足的营养摄入不仅对肿瘤细胞至关重要，对T细胞也是如此。T细胞的激活、分化和增殖伴随着增加的代谢需求。在肿瘤微环境中，肿瘤细胞在氨基酸摄取上具有竞争优势，这削弱了T细胞的功能。由于对氨基酸的依赖和成瘾，靶向氨基酸代谢代表着一种双重抗肿瘤效应，既抑制了癌细胞的恶性特性，又抑制了肿瘤源性免疫抑制。因此，鉴定胰腺导管腺癌中特定的氨基酸调控因子为治疗策略提供了新的见解。研究发现 02 在这项研究中，研究人员证明了PDAC组织中ALYREF的上调与不良预后和免疫逃逸有关。此外，ALYREF促进了PDAC细胞在体内外的增殖，并限制了CD8+T细胞的效应功能。从机理上讲，研究人员发现ALYREF特异性识别JunD mRNA上的m5C位点并维持其稳定性。随后，JunD转录激活SLC7A5，并进一步增强mTORC1信号的活性。此外，上调的SLC7A5促使PDAC细胞摄取过量氨基酸，同时破坏CD8+T细胞的代谢并限制其功能。这项研究揭示了m5C修饰、氨基酸运输和免疫微环境之间的关系。ALYREF可能是PDAC代谢脆弱性和免疫监视的一个新靶点。研究结果 03 综上所述，研究阐明了ALYREF的临床意义及其在人类PDAC中的致癌作用。ALYREF敲低通过损害JunD-SLC7A5-mTORC1轴抑制PDAC细胞增殖并减弱肿瘤免疫逃逸。这些发现为开发PDAC的潜在治疗策略提供了新的见解。参考资料：https://www.nature.com/articles/s41420-024-01862-2声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

信使RNA临床研究