Anti-Human/Monkey MDR-1 (CD243) [Clone UIC2] – Purified in vivo GOLD™ Functional Grade

Mouse Balb/c 3T3 fibroblasts transfected with human MDR1 cDNA

This monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Functional grade preclinical antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

Activity is directed against the extracellular domain of the Multidrug Resistance Protein 1 (MDR-1), also known as P-glycoprotein (P-gp) or CD243. Clone UIC2 is unique among anti-P-gp antibodies because its binding is conformation-sensitive; it preferentially recognizes the transporter in its physiological "active" state or when bound to substrates/modulators¹. It cross-reacts with MDR-1 from non-human primates, including Cynomolgus, Rhesus, and African Green monkeys².

MDR-1 (P-glycoprotein) is a 170 kDa ATP-dependent efflux pump belonging to the ABC transporter superfamily. It actively transports a wide variety of structurally diverse hydrophobic drugs (e.g., anthracyclines, vinca alkaloids, taxanes) out of cells, thereby reducing intracellular drug accumulation and causing chemotherapy resistance⁴.

Clone UIC2 was originally developed to inhibit this efflux function. Unlike other antibodies (such as MRK16) which bind P-gp but only weakly inhibit transport, UIC2 acts as a potent inhibitor of drug efflux, effectively reversing multidrug resistance in vitro and in xenograft models^1,5.

A defining characteristic of UIC2 is the "UIC2 Shift." The antibody recognizes a conformational epitope that becomes more accessible when the pump is frozen in a specific transition state—often induced by the binding of a substrate (like vinblastine) or ATP depletion⁶. This property allows researchers to use the "UIC2 Shift Assay" to not only detect the physical presence of P-gp but to actively measure its functional capacity and screen for substrates that induce this conformational change⁶.

MDR-1 is expressed on the apical surfaces of epithelial cells in the liver (bile canaliculi), kidney (proximal tubules), intestine, and blood-brain barrier, where it mediates the excretion of xenobiotics³. It is highly overexpressed in many multidrug-resistant tumors.

Transporter (Efflux pump)

1. Mechetner EB, Roninson IB. Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody. Proc Natl Acad Sci U S A. 89(13):5824-5828. 1992.
2. Szalóki G, Goda K, Tóth J, et al. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity. PLoS One. 9(9):e107875. 2014.
3. Gottesman MM, Fojo T, Bates SE. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2(1):48-58. 2002.
4. Ambudkar SV, Kimchi-Sarfaty C, Sauna ZE, Gottesman MM. P-glycoprotein: from genomics to mechanism. Oncogene. 22(47):7468-7485. 2003.
5. Mechetner EB, Schott B, Morse BS, et al. P-glycoprotein function involves conformational transitions detectable by differential immunoreactivity. Proc Natl Acad Sci U S A. 94(24):12908-12913. 1997.
6. Park SW, Silva M, Korsmeyer SJ, et al. Analysis of P-glycoprotein-mediated membrane transport in human peripheral blood lymphocytes using the UIC2 shift assay. Blood. 102(3):1003-1011. 2003.