December 19, 2018
SOLVO’s R&D team have been busy in recent months, adding new members of the SLC5A family to our growing portfolio of transporter services. We have now brought on board the fructose transporter SGLT5 and inositol transporter SGLT6, bringing the total number of human SGLTs in the portfolio to four – SGLT1, SGLT2, SGLT5, and SGLT6. We also continue to expand our range of preclinical animal models, and have also now launched services for dog Sglt2 and mouse Sglt2.
In addition, we have been focused on increasing the number of validated probe substrates for use with our existing transporter models, with an emphasis on clinically relevant drug substrates or endogenous molecules. As a result of these efforts we have now validated uric acid as a probe substrate for use with our OAT1, OAT2, OAT3 and OAT4 uptake transporter assays, as well as the BCRP efflux transporter vesicular transport assay. Creatinine can also now be utilized as a probe substrate in our OAT2 and OCT2 uptake transporter assays, while our MRP1 and MRP2 vesicular transport assays were validated with estradiol-17-beta-glucuronide and coproporphyrin I, respectively.
We have also now validated the use of three inhibitors for use with MDR1 or BCRP transport assessment using Caco-2 cells, in accordance with the latest FDA draft guidance of in vitro drug-drug interaction studies. Accordingly, three inhibitors can now be utilized for BCRP inhibition in this cell line: Ko143, novobiocin, and fumitremorgin C, whereas verapamil, PSC833 and ketoconazole can be used to inhibit MDR1.
This year proved to be a productive year for scientists working for SOLVO, with a major highlight in 2018 being the strengthening of collaborations with our transporter colleagues in industry and academia.
As a continuation of the study that characterized interaction of sodium-taurocholate co-transporting polypetide (NTCP) with bile salts/acids (Jani 2018 Toxicol In Vitro), we performed kinetic characterization of transport of bile salts/acids by organic anion transporting polypeptide 1B1 (OATP1B1). The work was carried out within the DILI (drug induced liver injury) consortium and was a joint effort of SOLVO as the leader of the project and colleagues from Servier, Glaxo Smithkline (GSK), Janssen as well as colleagues from the University of Liverpool (Toth 2018 Toxicol In Vitro).
Characterization of transport kinetics of rosuvastatin and olmesartan by rat Oatps as well as prediction of transporter-mediated drug-drug interaction (tDDI) due to inhibition of Oatps by drugs was the result of a productive collaboration with the University of Washington as the project leader and Roche as a big pharma partner ((a) Ishida 2018 Drug Metab Dispos; (b) Ishida 2018 Drug Metab Dispos).
Several studies highlighting the role of efflux transporters in absorption-distribution-excretion (ADE) properties of CHF6001, a novel PDE4 inhibitor developed by Chiesi Farmaceutici (Cenacchi 2018 Eur J Pharm Sci) and suggesting a likely role for BSEP in hepatotoxicity of TAK-875, a GPR40 agonist were the results of a collaboration with scientists in the service industry with DILISym Services playing the leading role together with colleagues from Takeda representing the pharma industry (Longo 2018 Toxicol Sci).
SOLVO as the project initiator and leader contributed significantly to inhibitor profiling of concentrative nucleoside transporters (CNTs) and equilibrative nucleoside transporters (ENTs). Scientists from the University of Barcelona and Virtuadrug contributed with modeling to the project (Vasko 2018 Xenobiotica).
Detailed characterization of cellular BCRP assays to highlight applicability and limitations of the assay systems was the topic of a collaboration with Sigma-Aldrich (Safar 2018 J Pharm Sci).
Multidrug resistance (MDR) mediated by efflux transporters has major clinical implications as demonstrated by more than thirty years ago. Nevertheless, reference values for activities of major MDR-ABC transporters (P-glycoprotein, BCRP, MRP1) in lymphocytes had not been published until our FACS study established the reference values for CD3+ lymphocytes in healthy volunteers (Szeremy 2018 Cytometry B). This study was carried out in collaboration with MDQuest and scientists from the University of Debrecen.
Keeping an open eye to academic science has always been a cornerstone of our research strategy. Collaborations with Semmelweis University scientists, and scientists from the Hungarian Academy of Sciences (HAS) on uptake transport of baicalin showed the applicability of our in vitro methodology to phytomedicines (Kalapos-Kovacs 2018 Phytother Res).
A collaboration initiated by scientists from the University of Szeged has revealed a complex transcriptional regulation of baculovirus transcription (Moldován 2018 Sci Rep).
The role of microRNAs is a hot topic in many fields of science. Our contribution to a project initiated by scientists from Semmelweis U and Óbuda U highlighted the complexity and regulatory role of miR206 in cancer (Mihaly 2018 Exp Biol Med (Maywood)).
We continue to be humbled by the attention and cooperativity we are getting from our industry and academic colleagues, and extend our sincere thanks to them for their contributions which play a major role in our R&D productivity.
As 2018 draws to a close, all of us at SOLVO would like to wish you all the best for the holiday season and a very happy and prosperous New Year. Looking forward to next year, 2019 promises to be a very special year for us as it will be SOLVO’s 20th anniversary! Since the company’s founding in 1999, we have strived to support the transporter and ADME-Tox field by developing the widest range of transporter products and services on the market. As the years have passed, we have seen how the field has grown and evolved, and are very proud of our role in this. With our 20th anniversary on the horizon we are excited to be a key part of the ADME-tox community and to make further contributions for the next 20 years and beyond! Stay connected to SOLVO to find out more about the events and special offers we have planned for this coming year, including two Meet the Experts conferences, further new product and service launches, an exciting program of webinars, and special offers throughout the year!
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