Last update 01 Nov 2024

SLCO3A1

Last update 01 Nov 2024

Basic Info

Synonyms

OATP-D, OATP-RP3, OATP3A1

+ [12]

Introduction

Putative organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormone L-thyroxine, prostanoids such as prostaglandin E1 and E2, bile acids such as taurocholate, glycolate and glycochenodeoxycholate and peptide hormones such as L-arginine vasopressin, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:14631946, PubMed:16971491, PubMed:19129463, PubMed:30063921). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable).

Drugs associated with SLCO3A1

Liposomal prostaglandin E-1

Target

SLCO3A1

Mechanism

SLCO3A1 agonists

Active Org.-

Originator Org.

Endovasc, Inc.

Active Indication

Pulmonary Veno-Occlusive Disease

Inactive Indication

Peripheral arterial occlusive disease

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

ONO-1404

Target

SLCO3A1

Mechanism

SLCO3A1 agonists

Active Org.-

Originator Org.

Ono Pharmaceutical Co., Ltd.

Active Indication-

Inactive Indication

Peripheral Vascular Diseases

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Ecraprost

Target

SLCO3A1

Mechanism

SLCO3A1 agonists

Active Org.-

Originator Org.

Mitsubishi Tanabe Pharma Corp.

Active Indication-

Inactive Indication

Chronic Limb-Threatening Ischemia [+1]

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with SLCO3A1

NCT03159559 / Unknown statusPhase 4IIT

A Randomized, Open-label Single-center Trial of Lipo-prostaglandin E1 Improves Coronary Microcirculation Dysfunction in Patients With Ischemic Heart Disease Combine With Diabetes Mellitus

This study is undertaken to determine if intravenous Lipo-PGE1 therapy would improve coronary microvascular perfusion in patients with ischemic heart disease by CMRI.

Start Date01 Jan 2017

Sponsor / Collaborator

Shanghai Tongji Hospital

NCT02338440 / Unknown statusPhase 2/3IIT

Pharmacokinetic Study of Lipo-PGE1 for Prevention of VOD After HSCT

Veno-occlusive disease (VOD) after hematopoietic stem cell transplantation (HSCT) remains the major complication. VOD occurs in 11-31% of pediatric HSCT and the mortality reaches up to 50%.
Prostaglandin E1 (PGE1) have been reported to prevent and relieve the severity of VOD by Gluckman et al.. Lipo-PGE1 is a transporter of PGE1, which is superior in concentrating PGE1 and acts for prolonged time. Because of the prolonged effective time, lipo-PGE1 acts comparable effects by 1/4
1/8 of PGE1 dose. Empirically, pediatric HSCT centers adopt lipo-PGE1 in dose of 1 mcg/kg/day (0.042 mcg/kg/hr), which is 1/7 of the dose recommended by Gluckman, et al. This prospective study will investigate the concentration of lipo-PGE1 with preventive lipo-PGE1 with empirical dose (1 mcg/kg/day).

Start Date01 Jan 2015

Sponsor / Collaborator

Seoul National University Hospital

NCT01245855 / Unknown statusPhase 3IIT

Protective Effect of Lipo-PGE1 on Myocardial Injury Following Percutaneous Coronary Intervention

we hypothesized that periprocedural treatment with intravenous lipo-PGE1 may reduce myocardial injury and improve clinical outcomes in patients undergoing PCI.

Start Date01 Jan 2011

Sponsor / Collaborator-

100 Clinical Results associated with SLCO3A1

100 Translational Medicine associated with SLCO3A1

0 Patents (Medical) associated with SLCO3A1

136

Literatures (Medical) associated with SLCO3A1

20 Aug 2024·Journal of the American Heart Association

Systematic Druggable Genome‐Wide Mendelian Randomization Identifies Therapeutic Targets for Functional Outcome After Ischemic Stroke

Article

Author: Zhu, Li‐Fang ; Dong, Ming‐Hao ; Tian, Dai‐Shi ; Chu, Yun‐Hui ; Zhang, Lu‐Yang ; Yang, Sheng ; Deng, Gang ; Shang, Ke ; Xiao, Jun ; Pang, Xiao‐Wei ; Zhou, Luo‐Qi ; Qin, Chuan ; Chen, Lian ; Wang, Wei ; You, Yun‐Fan

BackgroundStroke is a leading cause of death worldwide, with a lack of effective treatments for improving the prognosis. The aim of the present study was to identify novel therapeutic targets for functional outcome after ischemic stroke .Methods and Results Cis‐expression quantitative trait loci data for druggable genes were used as instrumental variables. The primary outcome was the modified Rankin Scale score at 3 months after ischemic stroke, evaluated as a dichotomous variable (3–6 versus 0–2) and also as an ordinal variable. Drug target Mendelian randomization, Steiger filtering analysis, and colocalization analysis were performed. Additionally, phenome‐wide Mendelian randomization analysis was performed to identify the safety of the drug target genes at the genetic level. Among >2600 druggable genes, genetically predicted expression of 16 genes ( ABCC2 , ATRAID , BLK , CD93 , CHST13 , NR1H3 , NRBP1 , PI3 , RIPK4 , SEMG1 , SLC22A4 , SLC22A5 , SLCO3A1 , TEK , TLR4 , and WNT10B ) demonstrated the causal associations with ordinal modified Rankin Scale ( P <1.892×10 −5 ) or poor functional outcome (modified Rankin Scale 3–6 versus 0–2, P <1.893×10 −5 ). Steiger filtering analysis suggested potential directional stability ( P <0.05). Colocalization analysis provided further support for the associations between genetically predicted expression of ABCC2 , NRBP1 , PI3 , and SEMG1 with functional outcome after ischemic stroke. Furthermore, phenome‐wide Mendelian randomization revealed additional beneficial indications and few potential safety concerns of therapeutics targeting ABCC2 , NRBP1 , PI3 , and SEMG1 , but the robustness of these results was limited by low power. ConclusionsThe present study revealed 4 candidate therapeutic targets for improving functional outcome after ischemic stroke, while the underlying mechanisms need further investigation.

01 Jul 2024·Molecular Pharmaceutics

Transporter Protein Expression of Corneal Epithelium in Rabbit and Porcine: Evaluation of Models for Ocular Drug Transport Study

Article

Author: Urtti, Arto ; Ramsay, Eva ; Terasaki, Tetsuya ; Kidron, Heidi ; Uchida, Yasuo ; Auriola, Seppo ; Montaser, Ahmed B. ; Niitsu, Kanako ; Huttunen, Kristiina M.

The transcorneal route is the main entry route for drugs to the intraocular parts, after topical administration. The outer surface, the corneal epithelium (CE), forms the rate-limiting barrier for drug permeability. Information about the role and protein expression of drug and amino acid transporter proteins in the CE is sparse and lacking. The aim of our study was to characterize transporter protein expression in rabbit and porcine CE to better understand potential drug and nutrient absorption after topical administration. Proteins, mainly Abc and Slc transporters, were characterized with quantitative targeted absolute proteomics and global untargeted proteomics methods. In the rabbit CE, 24 of 48 proteins were detected in the targeted approach, and 21 of these were quantified. In the porcine CE, 26 of 58 proteins were detected in the targeted approach, and 20 of these were quantified. Among these, 15 proteins were quantified in both animals: 4f2hc (Slc3a2), Aqp0, Asct1 (Slc1a4), Asct2 (Slc1a5), Glut1 (Slc2a1), Hmit (Slc2a13), Insr, Lat1 (Slc7a5), Mct1 (Slc16a1), Mct2 (Slc16a7), Mct4 (Slc16a3), Mrp 4 (Abcc4), Na⁺/K⁺-ATPase, Oatp3a1 (Slco3a1), and Snat2 (Slc38a2). Overall, the global proteomics results supported the targeted proteomics results. Organic anion transporting polypeptide Oatp3a1 was detected and quantified for the first time in both rabbit (1.4 ± 0.4 fmol/cm²) and porcine (11.1 ± 5.3 fmol/cm²) CE. High expression levels were observed for L-type amino acid transporter, Lat1, which was quantified with newly selected extracellular domain peptides in rabbit (48.9 ± 11.8 fmol/cm²) and porcine (37.6 ± 11.5 fmol/cm²) CE. The knowledge of transporter protein expression in ocular barriers is a key factor in the successful design of new ocular drugs, pharmacokinetic modeling, understanding ocular diseases, and the translation to human.

01 Dec 2023·Chemosphere

Organic anion transporting polypeptide 3a1 is a novel influx pump for Perfluorooctane sulfonate in Sertoli cells and contributes to its reproductive toxicity

Article

Author: Zhao, Nannan ; Ren, Hang ; Jiang, Lianlian ; Zheng, Shaokai ; Wang, Hongxia ; Qiu, Lianglin ; Qiu, Chong ; Li, Ting ; Lin, Xiaojun ; Huang, Jiyan

Persistent organic pollutant perfluorooctane sulfonate (PFOS) is strongly associated with male reproductive disorders, but the related mechanisms are still not fully understood. In this study, we used in vivo and in vitro models to explore the role of organic anion transporting polypeptide 3a1 (Oatp3a1) on PFOS-induced male reproductive injury. Thirty male C57BL/6 (B6) mice were orally given PFOS (0-10 mg/kg/bw) for 28 days. Body weight, organ index, sperm count, histology, and blood-testis barrier (BTB) integrity were evaluated. Primary Sertoli cells were used to describe the related molecular mechanisms of male reproductive injury caused by PFOS. Our results showed that PFOS induced a decrease in sperm count, morphological damage to testicular Sertoli cells, and disruption of BTB. In the in vitro model, exposure to PFOS significantly increased Oatp3a1 mRNA and protein levels and decreased miR-23a-3p expression in Sertoli cells, accompanied by reduced trans-epithelial electrical resistance (TEER) value. By performing the ¹⁴C-PFOS uptake experiment, we showed that ¹⁴C-PFOS uptake in HEK293-Oatp3a1 cells was apparently higher than in HEK293-MOCK cells. Meanwhile, treating Sertoli cells with Oatp3a1 siRNA significantly decreased Oatp3a1 expression and rescued PFOS-induced decreases in TEER value. As such, the present study highlights that Oatp3a1 may play an important role in the toxic effect of PFOS on Sertoli cells, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.

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SLCO3A1

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