MATE1 Inhibition Assessment Service

Unlocking Multidrug and Toxin Extrusion Protein 1 (MATE-1) Inhibition: Enhance Your ADME Insights

At Creative Biolabs, we are dedicated to delivering high-quality services of in vitro absorption, distribution, metabolism, and excretion (ADME), crucial for advancing cancer immunotherapy research. Our team leverages state-of-the-art methodologies to offer comprehensive insights into drug absorption, distribution, metabolism, and excretion profiles.

MATE-1 Inhibition Assay

MATE-1 mediates the active secretion of these compounds into the urine, aiding in their removal from the body. Understanding the function and inhibition of MATE-1 is essential for drug development, as inhibition can lead to altered pharmacokinetics and potential drug-drug interactions.

At Creative Biolabs, a cell-based assay is used to evaluate whether test compounds inhibit MATE-1. The assay is a functional, cell-based assay designed to assess antagonist activity, with an HPLC-MS/MS-based detection of MATE-1 by proprietary cell line (CHO-K1/HEK293) overexpressing MATE-1 to ensure the specificity of action by this transporter. We used metformin (a commonly used antidiabetic drug) as a probe substrate in this assay since it is a known substrate of MATE-1. The intracellular accumulation of metformin serves as the primary readout for transporter activity.

• The Principle of MATE-1 Inhibition Assay

The principle behind the assay is that if a test compound inhibits MATE-1, it will prevent the transporter from effluxing metformin out of the cells, leading to an increased intracellular accumulation of metformin. Therefore, the level of inhibition of the test compound is inversely proportional to the amount of metformin detected inside the cells. A higher intracellular metformin concentration indicates a stronger inhibitory effect of the test compound on MATE-1.

• The Procedure of MATE-1 Inhibition Assay

The procedure for the assay involves exposing the MATE-1 overexpressing cells to metformin in the presence of the test compound. LC-MS/MS is then used to precisely quantify the amount of metformin that has accumulated within the cells. LC-MS/MS is a highly sensitive technique that allows for the accurate measurement of small molecules within complex biological matrices.

Methods of DAPI Substrate Assay

Another substrate of MATE-1, 4',6-diamidino-2-phenylindole (DAPI), serves as a fluorescent substrate for MATE1 transporter activity, making it ideal for evaluating the inhibitory effects of potential inhibitors in MATE1 assays.

The methods of DAPI substrate assay are as follows:

• Preparation: Culturing kidney cell lines expressing MATE1.
• Incubation: Co-incubating cells with DAPI in the presence or absence of potential inhibitors.
• Fluorescence Detection: Measuring DAPI fluorescence intensity using a fluorescence plate reader to indicate cellular uptake.
• Data Analysis: Analyzing fluorescence data to determine the inhibitory effects of test compounds on MATE1 activity.

Advantages

• Precise Inhibition Assessment: Evaluate MATE1 inhibition potential accurately.
• Optimized Drug Development: Enhance therapeutic efficacy through refined ADME profiling.
• Accelerated Research: Expedite candidate selection and regulatory approval processes.

Contact Creative Biolabs today to leverage our specialized MATE1 inhibition assessment service. Our expertise and commitment to excellence ensure robust ADME evaluations, facilitating advancements in cancer immunotherapy research.

For Research Use Only | Not For Clinical Use