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The multidrug resistant phenotype of cancer cells can often result from the over-production of a number of ATP binding cassette (ABC) transporters, including P-glycoprotein (P-gp). These multi-drug efflux transporters expel administered anti-cancer drugs from the cancer cell, preventing sufficient intracellular drug accumulation and ultimately, drug efficacy. The co-administration of compounds that can impede the efflux of chemotherapeutic agents by these ABC-transporters can concomitantly modulate various cytochrome P450 (CYP450) enzymes, consequently impacting upon anti-cancer drug metabolism. This can further result in unfavourable drug-drug interactions and altered pharmacokinetic properties of the administered anti-cancer drugs with knock-on adverse cytotoxic side effects. This review will discuss some of the P-gp inhibitors designed and employed to date, as well as expressing our views of the shortcomings of their design strategy. We present a medicinal chemist's wish list for the paradigmatic P-gp inhibitor molecule and examine the possible future strategies that could be implemented to achieve its design.
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, UK. email@example.com.
This article was published in the following journal.
Name: Current drug metabolism
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A randomized trial assessing the impact of three different glycoprotein IIb/IIIa antagonists on glycoprotein IIb/IIIa platelet receptor inhibition and clinical endpoints in patients with acute coronary syndromes.
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To determine the local (cervico-vaginal) and systemic (whole body) safety of vaginal immunisation with ZM96gp140 glycoprotein administered 9 times over a 3 week period.
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A stochastic process such that the conditional probability distribution for a state at any future instant, given the present state, is unaffected by any additional knowledge of the past history of the system.
A course or method of action selected to guide and determine present and future decisions.
Decisions for determining and guiding present and future objectives from among alternatives.
A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions.
Decisions, usually developed by government policymakers, for determining present and future objectives pertaining to the health care system.
Cancer is not just one disease but many diseases. There are more than 100 different types of cancer. Most cancers are named for the organ or type of cell in which they start - for example, cancer that begins in the colon is called colon cancer; cancer th...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
Head and neck cancers
Cancer can occur in any of the tissues or organs in the head and neck. There are over 30 different places that cancer can develop in the head and neck area. Mouth cancers (oral cancers) - Mouth cancer can develop on the lip, the tongue, the floor...