At the simplest level, all known living organisms are comprised of cells- microscopic compartments containing all the necessary biological machinery needed to sustain life. The defining characteristic of a cell is that the inner components are physically separated from the outside environment, a function achieved by a cell membrane consisting predominantly of phospholipids. While this phospholipid surface allows some chemical compounds into the cell (these are termed permeable compounds), many others (impermeable compounds) cannot cross without the assistance of specialized proteins embedded into the cell membrane, called membrane transport proteins or transporters. SOLVO Biotechnology is the leading transporter-focused biotechnology company, and a pioneer in the application of transporter biology to the process of drug discovery.
In humans and other multicellular organisms, transporters often play an important role at so-called barrier sites: points which organs or blood form an interface with each other, or with an external space. Examples of this include the blood-brain barrier, the placenta (maternal-fetal barrier), and the intestine. In addition, they function to help remove substances from the body (excretion) via detoxification organs such as the kidneys and liver.
Transporters can function in two ways- by enabling the selective passage of compounds into the cell, also referred to as uptake, and by removing compound out of the cell into the extracellular milieu, a process known as efflux. These uptake and efflux transporters often work together, for example in the liver, where compounds can be taken up from one extracellular compartment (the blood) into liver cells by uptake transporters, and then removed from the same cell into a different extracellular compartment (the bile) by efflux transporters, where it is excreted from the body in feces.
Transporters present in liver cells (hepatocytes). Uptake transporters (inward-facing arrows) enable substances to be taken up from the blood into the hepatocyte, while efflux transporters (outward facing arrows) pump substances out of the hepatocyte into either the blood, or the bile canaliculus (shown in green), from where they are excreted in the feces. Also shown are equilibrative transporters (two-sided arrow), which can allow substances to pass in either direction, from a high concentration to a low concentration.
Because of their importance in enabling the passage of substances into and out of the body, as well as individual organs, it is increasingly recognized that transporters play an important role in the ADME-Tox (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profile of many therapeutic drugs. In addition, when multiple drugs are taken at the same time, there is the potential for one drug to interfere with the transport of another drug, changing the amount that is present in the circulation, is removed from the body, or even the amount that reaches a particular organ such as the brain. This is referred to as drug-drug interaction (DDI), and be dangerous or even fatal to patients from both increased side effects (toxicity), or reduced pharmacological effect (lack of efficacy). In addition, many transporters facilitate the movement of hormones, proteins, lipids, and other endogenous compounds across the cell membrane, and so drugs which inhibit these transport processes can prevent normal biological function, leading to toxicity.
In recent years regulatory agencies in Europe (European Medicines Agency; EMA), the US (Food and Drug Administration; FDA), and Japan (Pharmaceuticals and Medical Devices Agency; PMDA) have all brought out recommendations and guidelines for pharmaceutical and biotech companies developing new drugs, in which they suggest carrying out studies involving transporters in order to establish the potential for DDIs.
SOLVO Biotechnology works with pharmaceutical and biotech companies developing new drugs, and enables them to investigate the potential for DDIs. Since the company’s inception in 1999, they have produced over 200 experimental assays to investigate the function of transporters. As a contract research organization (CRO) SOLVO conducts many of these experiments in-house, in addition to selling the assays and reagents to others in order to enable them to carry out their own experiments. The success of the company is reflected in the statistic that it serves over 450 customers in 40 different countries, including the vast majority of the world’s largest pharmaceutical and biotechnology companies. They have recently entered into a North American distribution deal for their products with Sigma-Aldrich, one of the largest global specialty chemical and biochemical companies, adding to their current distribution partnerships with Tebu-bio (Europe), Biogenuix Medsystems (India), and KAC (Japan). In addition to their main sites in Budaörs and Szeged, Hungary, SOLVO representatives can now be found in locations as far afield as Bangalore, India, and Seattle, San Francisco, and Boston in the United States.
As a company that built on the back of basic research, SOLVO has continued to invest in transporter science, with researchers at the company authoring over 50 peer-reviewed journal articles to date. It is this focus on innovation and continuous improvement that enables the company to stay ahead of the competition. It also drives the development of new products and services, with around 10-15 new assays launched every year. From the study of individual transporters, to in vitro cell-based models of important barrier organs such as the liver or kidney, through to positron emission tomography (PET) imaging of whole animals, SOLVO Biotechnology provides a one-stop solution to transporter-related questions in drug discovery and development.