Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multidrug resistance (MDR) is a unique phenomenon in cancer patients and is commonly associated with an overexpression of the human MDR gene mdr1, which encodes an energy-dependent Mr 180 kDa membrane bound protein, known as P-glycoprotein. P-glycoprotein serves as a membrane efflux to pump the drugs out of the cancer cells. Western blot analysis, using a newly generated monoclonal antibody F4 which recognizes specifically an extracellular epitope of human MDR1 P-glycoprotein, reveals that soluble P-glycoprotein is detected in the cultured media of viable adriamycin-resistant human ovarian carcinoma 2780AD cells, whereas those of the drug-sensitive parent A2780 cells contain no detectable level of soluble P-glycoprotein. Soluble P-glycoprotein also is detected in extracellular fluids of cancer patients, such as malignant ascites and serum, and is not detectable in serum samples of normal healthy individuals. The Mr of soluble P-glycoprotein is the same as that of membrane bound P-glycoprotein. The presence of soluble P-glycoprotein in extracellular fluids may provide the basis for its use as a quantitative parameter of MDR and as a means to lessen or reverse MDR.
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PMID:Detection of soluble P-glycoprotein in culture media and extracellular fluids. 791 20

Novel pyrimidinyl pyrazole derivatives were synthesized and examined for cytotoxic and antitumor activity. Mannich reaction was employed to construct this scaffold. Among the compounds synthesized, a series of propene derivatives exhibited a potent cytotoxic activity against some tumor cell lines including multidrug resistant cell lines due to the overexpression of P-glycoprotein. The vinyl bond moiety in the scaffold was believed to be required for the cytotoxic activity. Among them, compound 14 g, when administered intraperitoneally, showed potent antitumor activity against the malignant ascites caused by intraperitoneal inoculation of P388 cells in mice. This compound also showed high activity against a solid tumor Meth A mouse fibrosarcoma when administered both intraperitoneally and orally.
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PMID:Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. 1074 12