Transporter Drug Discovery Assays and Products
Understanding the function of membrane transporters in medication efficacy and safety has recently advanced. For instance, the human genome contains annotations for more than 400 membrane transporters in two significant superfamilies: ATP-binding cassette and solute carrier. Numerous of these transporters have been identified, cloned, and localized in human tissues and cellular membrane domains. Particular focus has been placed on transporters expressed in the endothelium of the blood-brain barrier, the epithelia of the intestine, liver, and kidney. The interaction of medicines and their metabolites with mammalian transporters found in epithelial and endothelial barriers is currently the subject of a vast body of study.
Fig.1 Selected human transport proteins for drugs and endogenous substances. (The International Transporter Consortium, 2010)
Creative Biolabs offers high-quality transporter assays and products to help research groups accelerate drug discovery and development.
The movement of ions, tiny compounds, and macromolecules like proteins across a biological membrane is facilitated by a membrane protein known as a transporter. Molecules may be transported by the transporters through assisted diffusion or active transport. Creative Biolabs provides transporter in vitro assays to evaluate the therapeutic effects of your candidate against the targets.
Transport proteins may represent ideal targets for therapeutic or clinical intervention in a wide variety of diseases, Creative Biolabs offers transporter cell lines for our global clients.
Membrane transporters help cells function properly, aid in nutrient sensing, and have been connected to a number of diseases, such as cancer and obesity. For the purpose of enabling the research of transporters, Creative Biolabs provides quality-assured frozen membranes from cells expressing native or recombinant transporters.
Methods for Studying Transporters
- Membrane‑based assay systems
ATPase assay: By doing a colorimetric measurement of inorganic phosphate released during the transport process, substrate-dependent ATP hydrolysis has been utilized to assess the interactions of substrates and inhibitors with various ABC transporters. This assay's ease of use makes it a useful method that may be applied in high-throughput assays to screen for drugs that interact with specific ABC transporters.
Membrane vesicle transport assay: The efflux transporter activity of ABC transporters, in particular, has been studied using inverted plasma membrane vesicles. A wide range of cell lines, including drug-selected cells, transfected cells, and insect cells infected with baculovirus, have been utilized to create membrane vesicles.
- Cell‑based assay systems
Drug discovery techniques can use cell-based assay systems to find substrates and inhibitors for specific transporters as well as to create QSAR models. Additionally, mechanistic studies to evaluate transport processes, the rate-limiting phase in trans-epithelial transport, and transporter-based DDIs can be performed using these systems. It is frequently helpful to validate the engagement of a transporter with a probable substrate using data from different experimental settings.
- Intact organ/in vivo models
In recent years, numerous animal models with naturally occurring transporter deficiencies and transporter-gene knockouts have been identified, and their commercial accessibility has been rapidly rising. The function of transporters in physiology, the defense of important blood-tissue barriers, and the absorption and excretion of xenobiotics and endogenous substances have all been demonstrated through knockout models.
Reference
- The International Transporter Consortium. Membrane transporters in drug development. Nat Rev Drug Discov. 2010, 9: 215–236.
