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In the early discovery and development phase, drug candidates need to be screened for the cell permeability efficacy to evaluate the absorption potential. With the advanced one-stop PROTAC service platform, Creative Biolabs now provides comprehensive cell permeability assays for PROTAC candidates.
Drug absorption is to measure the movement of the compound into the bloodstream. For oral treatment, the drug is transported into blood via the intestinal pathway. For other treatments, such as intramuscular injection, intravenous therapy, etc., the drug is straightforward to blood. The capacity of cell permeability is a key factor to influence drug absorption and distribution. If a drug wants to enter into the systemic circulation, it needs to cross cell membranes through passive diffusion, active transport, etc. Poor permeability may be caused by the physicochemical properties of candidate drugs and membrane-based efflux mechanisms.
PROTAC application is critically limited by permeability, hence, monitoring cell permeability efficacy of PROTAC candidate is essential prior to subsequent functional assays. Creative Biolabs offers our clients with the following in vitro assays to determine the permeability.
PAMPA is an in vitro model of passive, transcellular permeation which can be used to determine the permeability of PROTACs over a large pH range. It has been widely used as a high throughput permeability assay to predict drug absorption in the pharmaceutical industries. A lipid-infused artificial membrane is utilized to act as a supplement to mediate the permeability assay. Creative Biolabs is dedicated to this assay through which PROTACs are added to the donor compartment and permeating an artificial hexadecane membrane to the acceptor compartment. We provide the results quantified by LC-MS/MS.
Fig.1 The schematic diagram of PAMPA model.
The Caco-2 permeability assay utilizes Caco-2 cell line derived from human colon carcinoma. This cell line has many characteristics that resemble intestinal epithelial cells including the formation of a polarized monolayer, intercellular tight junctions and well-defined brush border on the apical surface. This assay offers a measure of the permeability of PROTACs across the intestinal barrier. It's a mature method to investigate human intestinal permeability and drug efflux. The rate of transporting of PROTACs across the Caco-2 cell is assessed in both directions. Creative Biolabs delivers a highly automated and efficient Caco-2 permeability assay to determine the permeability and absorption of PROTACs.
Fig.2 The schematic diagram of Caco-2 permeability assay.
The MDCK cell is an epithelial cell line which is derived from canine kidney origin. The expression of transporter proteins and metabolic activity are low for MDCK cell. Compared to Caco-2 cell, MDCK cell proliferates and differentiates more quickly. Hence, it becomes an attractive alternative assay compared to Caco-2 permeability assay to assess the human intestine barrier. Creative Biolabs provides reliable MDCK and MDR1-MDCK permeability assays to determine the permeability of PROTACs.
Fig.3 The schematic diagram of MDCK permeability assay.
With experienced scientists and over a decade of exploration in the field of drug discovery and development, Creative Biolabs has established a one-stop PROTAC service platform to assist our clients to maximize the success of projects. We are committed to tailoring the optimal assay to fulfill your needs. Please contact us for more information and a detailed quote.