OBJECTIVES We endeavored to determine under what conditions a strategy of upstream use of small molecule platelet glycoprotein (GP) IIb/IIIa inhibitors for all acute coronary syndromes (ACS) patients is cost effective compared to that of selective use of abciximab in only those patients requiring percutaneous coronary intervention (PCI). BACKGROUND Small molecule GP IIb/IIIa inhibitors have s...

We previously reported that exposure of human colon adenocarcinoma (Caco-2) cells to the bitter substance phenylthiocarbamide (PTC) rapidly enhanced transport function P-glycoprotein (P-gp). In this study, we investigated short-term effect etoposide, another bitter-tasting P-gp substrate, on in same cell line. found etoposide significantly increased both protein level plasma membrane fraction a...

Mouse mammary tumor virus-producing cultures of mouse mammary tumor cells synthesize a viral-related polypeptide of molecular weight of 73,000 (gp 73) which is rapidly labeled during a short pulse but disappears during the chase concomitantly with the appearance of label in the virion glycoproteins gp 49 and gp 37.5/33.5. The addition of the protein synthesis-inhibitor cycloheximide to the chas...

The effectiveness of Hsp90 inhibitors as anticancer agents was limited in multidrug-resistant (MDR) human cancer cells due to induction of heat shock proteins (Hsps) such as Hsp70/Hsp27 and P-glycoprotein (P-gp)-mediated efflux. In the present study, we showed that resistance to Hsp90 inhibitors of MDR human cancer cells could be overcome with SIRT1 inhibition. SIRT1 knock-down or SIRT1 inhibit...

To support drug development and registration, Caco-2 cell monolayer assays have previously been set up and validated to determine whether candidate drugs are substrates or inhibitors of human P-glycoprotein (P-gp). In this study, the drug-drug interaction (DDI) potential of N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[4-methanesulfonylphenyl]propyl}piperidin-4-yl)-N-ethyl-2-[4-methanesulfonylphenyl]ace...

P-glycoprotein (P-gp) is the most studied ATP-binding cassette transporter, known to be able to cause multidrug resistance. The relevance of P-gp for clinical drug resistance remains controversial, however. Using our K14cre;Brca1F/F;p53F/F conditional mouse model of hereditary breast cancer, we previously found that modestly elevated expression levels of the mouse P-gp genes Mdr1a (Abcb1a) and/...

Iptacopan (LNP023) is a first-in-class, oral, low molecular weight, Factor B inhibitor being developed for the treatment of diseases associated with activation alternative complement pathway. Current Phase III studies iptacopan include paroxysmal nocturnal hemoglobinuria, C3 glomerulonephritis, IgA nephropathy, and atypical hemolytic uremic syndrome. Preclinical identified CYP2C8, OATP P-gp as ...

NSAIDs (non-steroidal anti-inflammatory drugs) have potential use as anticancer agents, either alone or in combination with other cancer therapies. We found that NSAIDs including celecoxib (CCB) and ibuprofen (IBU) significantly potentiated the cytotoxicity of Hsp90 inhibitors in human multidrug-resistant (MDR) cells expressing high levels of mutant p53 (mutp53) protein and P-glycoprotein (P-gp...

This study investigated the effects of racemic methadone (MET) on P-glycoprotein (P-gp) activity in cell culture. MET showed no differential rates of passage between the basolateral to apical (B to A) and apical to basolateral (A to B) direction across Caco-2 cell monolayers in a transwell system. MET transport in either direction was not importantly influenced by the P-gp inhibitor verapamil. ...

A glycoprotein (GP) which is immunochemically and biologically related to human prostatic acid phosphatase (PAP) has been isolated from human seminal plasma by ammonium sulfate precipitation followed by sequential concanavalin A:Sepharose 4B column, anion-exchange chromatography and gel filtration. The purified GP was shown to be homogeneous by disc- and sodium dodecyl sulfate: polyacrylamide g...