FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2002083676> ?p ?o ?g. }

• W2002083676 endingPage "384" @default.
• W2002083676 startingPage "376" @default.
• W2002083676 abstract "Kinase inhibition is an increasingly popular strategy for pharmacotherapy of human diseases. Although many of these agents have been described as “targeted therapy”, they will typically inhibit multiple kinases with varying potency. Pre-clinical model testing has not predicted the numerous significant toxicities identified during clinical development. The purpose of this study was to develop a bioinformatics-based method to predict specific adverse events (AEs) in humans associated with the inhibition of particular kinase targets (KTs). The AE frequencies of protein kinase inhibitors (PKIs) were curated from three sources (PubMed, Thompson Physician Desk Reference and PharmGKB), and affinities of 38 PKIs for 317 kinases, representing >50% of the predicted human kinome, were collected from published in vitro assay results. A novel quantitative computational method was developed to predict associations between KTs and AEs that included a whole panel of 71 AEs and 20 PKIs targeting 266 distinct kinases with Kd < 10 μM. The method calculated an unbiased, kinome-wide association score via linear algebra on (i) the normalized frequencies of AEs associated with 20 PKIs and (ii) the negative log-transformed dissociation constant of kinases targeted by these PKIs. Finally, a reference standard was calculated by applying Fisher’s exact test to the co-occurrence of indexed Pubmed terms (p ⩽ 0.05, and manually verified) for AE and associated kinase targets (AE–KT) pairs from standard literature search techniques. We also evaluated the enrichment of predictions between the quantitative method and the literature search by Fisher’s exact testing. We identified significant associations among already empirically well established pairs of AEs (e.g. diarrhea and rash) and KTs (e.g. EGFR). The following less well recognized AE–KT pairs had similar association scores: diarrhea-(DDR1;ERBB4), rash-ERBB4, and fatigue-(CSF1R;KIT). With no filtering, the association score identified 41 prioritized associations involving 7 AEs and 19 KTs. Among them, eight associations were reported in the literature review. There were only 78 out of a total of 4522 AE–KT pairs meeting the evaluation threshold, indicating a strong association between the predicted and the text mined AE–KT pairs (p = 3 × 10−7). As many of these drugs remain in development, a larger volume of more detailed data on AE–PKI associations is accessible only through non-public databases. These prediction models will be refined with these data and validated through dedicated prospective human studies. Our in silico method can predict associations between kinase targets and AE frequencies in human patients. Refining this method should lead to improved clinical development of protein kinase inhibitors, a large new class of therapeutics. http://www.lussierlab.org/publication/PAS/." @default.
• W2002083676 created "2016-06-24" @default.
• W2002083676 creator A5013944987 @default.
• W2002083676 creator A5036578095 @default.
• W2002083676 creator A5044514129 @default.
• W2002083676 creator A5058748971 @default.
• W2002083676 creator A5074706648 @default.
• W2002083676 creator A5079231875 @default.
• W2002083676 date "2010-06-01" @default.
• W2002083676 modified "2023-10-14" @default.
• W2002083676 title "Kinase inhibition-related adverse events predicted from in vitro kinome and clinical trial data" @default.
• W2002083676 cites W1544009106 @default.
• W2002083676 cites W1661470104 @default.
• W2002083676 cites W1968151389 @default.
• W2002083676 cites W1973174482 @default.
• W2002083676 cites W1998990808 @default.
• W2002083676 cites W2012223636 @default.
• W2002083676 cites W2016610112 @default.
• W2002083676 cites W2030205108 @default.
• W2002083676 cites W2031939751 @default.
• W2002083676 cites W2033853342 @default.
• W2002083676 cites W2035088488 @default.
• W2002083676 cites W2040135138 @default.
• W2002083676 cites W2048818283 @default.
• W2002083676 cites W2079428107 @default.
• W2002083676 cites W2096814387 @default.
• W2002083676 cites W2100772783 @default.
• W2002083676 cites W2101638297 @default.
• W2002083676 cites W2105381419 @default.
• W2002083676 cites W2107268345 @default.
• W2002083676 cites W2114578638 @default.
• W2002083676 cites W2114627676 @default.
• W2002083676 cites W2125905177 @default.
• W2002083676 cites W2126372889 @default.
• W2002083676 cites W2131347449 @default.
• W2002083676 cites W2138024326 @default.
• W2002083676 cites W2138512826 @default.
• W2002083676 cites W2150948412 @default.
• W2002083676 cites W2154896031 @default.
• W2002083676 cites W2290195878 @default.
• W2002083676 doi "https://doi.org/10.1016/j.jbi.2010.04.006" @default.
• W2002083676 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2893391" @default.
• W2002083676 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20434586" @default.
• W2002083676 hasPublicationYear "2010" @default.
• W2002083676 type Work @default.
• W2002083676 sameAs 2002083676 @default.
• W2002083676 citedByCount "30" @default.
• W2002083676 countsByYear W20020836762012 @default.
• W2002083676 countsByYear W20020836762013 @default.
• W2002083676 countsByYear W20020836762014 @default.
• W2002083676 countsByYear W20020836762015 @default.
• W2002083676 countsByYear W20020836762016 @default.
• W2002083676 countsByYear W20020836762020 @default.
• W2002083676 countsByYear W20020836762022 @default.
• W2002083676 crossrefType "journal-article" @default.
• W2002083676 hasAuthorship W2002083676A5013944987 @default.
• W2002083676 hasAuthorship W2002083676A5036578095 @default.
• W2002083676 hasAuthorship W2002083676A5044514129 @default.
• W2002083676 hasAuthorship W2002083676A5058748971 @default.
• W2002083676 hasAuthorship W2002083676A5074706648 @default.
• W2002083676 hasAuthorship W2002083676A5079231875 @default.
• W2002083676 hasBestOaLocation W20020836762 @default.
• W2002083676 hasConcept C184235292 @default.
• W2002083676 hasConcept C41008148 @default.
• W2002083676 hasConcept C54174078 @default.
• W2002083676 hasConcept C55493867 @default.
• W2002083676 hasConcept C60644358 @default.
• W2002083676 hasConcept C70721500 @default.
• W2002083676 hasConcept C74187038 @default.
• W2002083676 hasConcept C86803240 @default.
• W2002083676 hasConceptScore W2002083676C184235292 @default.
• W2002083676 hasConceptScore W2002083676C41008148 @default.
• W2002083676 hasConceptScore W2002083676C54174078 @default.
• W2002083676 hasConceptScore W2002083676C55493867 @default.
• W2002083676 hasConceptScore W2002083676C60644358 @default.
• W2002083676 hasConceptScore W2002083676C70721500 @default.
• W2002083676 hasConceptScore W2002083676C74187038 @default.
• W2002083676 hasConceptScore W2002083676C86803240 @default.
• W2002083676 hasFunder F4320321001 @default.
• W2002083676 hasIssue "3" @default.
• W2002083676 hasLocation W20020836761 @default.
• W2002083676 hasLocation W20020836762 @default.
• W2002083676 hasLocation W20020836763 @default.
• W2002083676 hasLocation W20020836764 @default.
• W2002083676 hasOpenAccess W2002083676 @default.
• W2002083676 hasPrimaryLocation W20020836761 @default.
• W2002083676 hasRelatedWork W1989116199 @default.
• W2002083676 hasRelatedWork W2608811481 @default.
• W2002083676 hasRelatedWork W2913045465 @default.
• W2002083676 hasRelatedWork W2925167008 @default.
• W2002083676 hasRelatedWork W2948125847 @default.
• W2002083676 hasRelatedWork W2991424847 @default.
• W2002083676 hasRelatedWork W3035584768 @default.
• W2002083676 hasRelatedWork W3043167921 @default.
• W2002083676 hasRelatedWork W3088289817 @default.
• W2002083676 hasRelatedWork W3125335171 @default.
• W2002083676 hasVolume "43" @default.
• W2002083676 isParatext "false" @default.

• next