About: Generating Inhibitors of P-Glycoprotein: Where to, Now?

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: Generating Inhibitors of P-Glycoprotein: Where to, Now? Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Generating Inhibitors of P-Glycoprotein: Where to, Now?
Creator	Callaghan, Richard Crowley, Emily Mcdevitt, Christopher
source	PMC
abstract	The prominent role for the drug efflux pump ABCB1 (P-glycoprotein) in mediating resistance to chemotherapy was first suggested in 1976 and sparked an incredible drive to restore the efficacy of anticancer drugs. Achieving this goal seemed inevitable in 1982 when a series of calcium channel blockers were demonstrated to restore the efficacy of chemotherapy agents. A large number of other compounds have since been demonstrated to restore chemotherapeutic sensitivity in cancer cells or tissues. Where do we stand almost three decades since the first reports of ABCB1 inhibition? Unfortunately, in the aftermath of extensive fundamental and clinical research efforts the situation remains gloomy. Only a small handful of compounds have reached late stage clinical trials and none are in routine clinical usage to circumvent chemoresistance. Why has the translation process been so ineffective? One factor is the multifactorial nature of drug resistance inherent to cancer tissues; ABCB1 is not the sole factor. However, expression of ABCB1 remains a significant negative prognostic indicator and is closely associated with poor response to chemotherapy in many cancer types. The main difficulties with restoration of sensitivity to chemotherapy reside with poor properties of the ABCB1 inhibitors: (1) low selectivity to ABCB1, (2) poor potency to inhibit ABCB1, (3) inherent toxicity and/or (4) adverse pharmacokinetic interactions with anticancer drugs. Despite these difficulties, there is a clear requirement for effective inhibitors and to date the strategies for generating such compounds have involved serendipity or simple chemical syntheses. This chapter outlines more sophisticated approaches making use of bioinformatics, combinatorial chemistry and structure informed drug design. Generating a new arsenal of potent and selective ABCB1 inhibitors offers the promise of restoring the efficacy of a key weapon in cancer treatment – chemotherapy.
has issue date	2009-10-05(xsd:dateTime)
bibo:doi	10.1007/978-1-60761-416-6_18
bibo:pmid	19949934
has license	no-cc
sha1sum (hex)	3dbcc029cf2eac4ce4b6684fc2f1f7f06312c53e
schema:url	https://doi.org/10.1007/978-1-60761-416-6_18
resource representing a document's title	Generating Inhibitors of P-Glycoprotein: Where to, Now?
has PubMed Central identifier	PMC7121335
has PubMed identifier	19949934
schema:publication	Multi-Drug Resistance in Cancer
resource representing a document's body	covid:3dbcc029cf2eac4ce4b6684fc2f1f7f06312c53e#body_text
is schema:about of	named entity 'resistance' named entity 'indicator' named entity 'chemical syntheses' named entity 'cancer' named entity 'potent' named entity 'However' named entity 'EFFECTIVE' named entity 'TISSUES' named entity 'SELECTIVE' named entity 'FACTOR' named entity 'CLINICAL' named entity 'PROMINENT' named entity 'NEW' named entity 'DEMONSTRATED' named entity 'EFFICACY' named entity 'RESPONSE TO CHEMOTHERAPY' named entity 'NATURE' named entity 'DATE' named entity 'GENERATING' named entity 'CHAPTER' named entity 'structure' named entity 'adverse' named entity 'sensitivity' named entity 'inhibition' named entity 'Despite' named entity 'toxicity' named entity 'ABCB1' named entity 'remains' named entity 'inhibit' named entity 'chemotherapy' named entity 'agents' named entity 'remains' named entity 'inhibitors' named entity 'ABCB1' named entity 'chemotherapy' named entity 'clinical research' named entity 'ABCB1' named entity 'chemotherapy' named entity 'ABCB1' named entity 'bioinformatics' named entity 'substrate' named entity 'chemotherapeutic' named entity 'ABCB1' named entity 'solubilities' named entity 'pharmacophore' named entity 'substrate' named entity 'structure based drug design' named entity 'nucleotide-binding domain' named entity 'efflux pumps' named entity 'potency' named entity 'cyclosporin' named entity 'translocation' named entity 'substrates' named entity 'binding sites' named entity 'ABCB1' named entity 'ABCB1' named entity 'binding site' named entity 'pharmacokinetic interactions' named entity 'protein' named entity 'matrix-assisted laser desorption' named entity 'clinical trials' named entity 'TMDs' named entity 'ABCB1' named entity 'substrate' named entity 'reserpine' named entity 'flupentixol' named entity 'genotoxic' named entity 'ABCB1' named entity 'interact' named entity 'neuraminidase' named entity 'ABCB1' named entity 'refractory' named entity 'drug resistance' named entity 'conformational flexibility' named entity 'pharmacophore' named entity 'interact' named entity 'holy grail' named entity 'cytochrome P450' named entity 'ligand'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software