Matches in SemOpenAlex for { <https://semopenalex.org/work/W2901280873> ?p ?o ?g. }
- W2901280873 endingPage "1137" @default.
- W2901280873 startingPage "1125" @default.
- W2901280873 abstract "Genetic mutations in the phosphatase PTPN11 (SHP2) are associated with childhood leukemias. These mutations cause hyperactivation of SHP2 due to the disruption of the autoinhibitory conformation. By targeting the activation-associated protein conformational change, we have identified an SHP2 inhibitor ( E)-1-(1-(5-(3-(2,4-dichlorophenyl)acryloyl)-2-ethoxy-4-hydroxybenzyl)-1,2,5,6-tetrahydropyridin-3-yl)-1 H-benzo[ d]imidazol-2(3 H)-one (LY6, 1) using computer-aided drug design database screening combined with cell-based assays. This compound inhibited SHP2 with an IC50 value of 9.8 μM, 7-fold more selective for SHP2 than the highly related SHP1. Fluorescence titration, thermal shift, and microscale thermophoresis quantitative binding assays confirmed its direct binding to SHP2. This compound was further verified to effectively inhibit SHP2-mediated cell signaling and proliferation. Furthermore, mouse and patient leukemia cells with PTPN11 activating mutations were more sensitive to this inhibitor than wild-type cells. This small molecule SHP2 inhibitor has a potential to serve as a lead compound for further optimization studies to develop novel anti-SHP2 therapeutic agents." @default.
- W2901280873 created "2018-11-29" @default.
- W2901280873 creator A5000645986 @default.
- W2901280873 creator A5010840699 @default.
- W2901280873 creator A5027835055 @default.
- W2901280873 creator A5029196561 @default.
- W2901280873 creator A5029323907 @default.
- W2901280873 creator A5034051890 @default.
- W2901280873 creator A5044668501 @default.
- W2901280873 creator A5071037763 @default.
- W2901280873 creator A5079330223 @default.
- W2901280873 creator A5085618254 @default.
- W2901280873 creator A5087515662 @default.
- W2901280873 date "2018-11-20" @default.
- W2901280873 modified "2023-09-27" @default.
- W2901280873 title "Small Molecule Inhibitor that Stabilizes the Autoinhibited Conformation of the Oncogenic Tyrosine Phosphatase SHP2" @default.
- W2901280873 cites W1488372279 @default.
- W2901280873 cites W1594662318 @default.
- W2901280873 cites W1965929992 @default.
- W2901280873 cites W1969918683 @default.
- W2901280873 cites W1986384270 @default.
- W2901280873 cites W1988963123 @default.
- W2901280873 cites W1999863487 @default.
- W2901280873 cites W2000813775 @default.
- W2901280873 cites W2014005478 @default.
- W2901280873 cites W2021832765 @default.
- W2901280873 cites W2024352432 @default.
- W2901280873 cites W2024837443 @default.
- W2901280873 cites W2030884611 @default.
- W2901280873 cites W2031168104 @default.
- W2901280873 cites W2032044839 @default.
- W2901280873 cites W2043160859 @default.
- W2901280873 cites W2043509228 @default.
- W2901280873 cites W2045979867 @default.
- W2901280873 cites W2047132220 @default.
- W2901280873 cites W2048864213 @default.
- W2901280873 cites W2068504978 @default.
- W2901280873 cites W2072037914 @default.
- W2901280873 cites W2079029484 @default.
- W2901280873 cites W2082448876 @default.
- W2901280873 cites W2085581188 @default.
- W2901280873 cites W2092511209 @default.
- W2901280873 cites W2093762625 @default.
- W2901280873 cites W2094548766 @default.
- W2901280873 cites W2102377211 @default.
- W2901280873 cites W2105606183 @default.
- W2901280873 cites W2113349387 @default.
- W2901280873 cites W2114367386 @default.
- W2901280873 cites W2121539092 @default.
- W2901280873 cites W2129595021 @default.
- W2901280873 cites W2130526419 @default.
- W2901280873 cites W2132298090 @default.
- W2901280873 cites W2144844081 @default.
- W2901280873 cites W2149312624 @default.
- W2901280873 cites W220016304 @default.
- W2901280873 cites W2322808186 @default.
- W2901280873 cites W2468923062 @default.
- W2901280873 cites W2475259576 @default.
- W2901280873 cites W2781625157 @default.
- W2901280873 doi "https://doi.org/10.1021/acs.jmedchem.8b00513" @default.
- W2901280873 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6467801" @default.
- W2901280873 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30457860" @default.
- W2901280873 hasPublicationYear "2018" @default.
- W2901280873 type Work @default.
- W2901280873 sameAs 2901280873 @default.
- W2901280873 citedByCount "35" @default.
- W2901280873 countsByYear W29012808732019 @default.
- W2901280873 countsByYear W29012808732020 @default.
- W2901280873 countsByYear W29012808732021 @default.
- W2901280873 countsByYear W29012808732022 @default.
- W2901280873 countsByYear W29012808732023 @default.
- W2901280873 crossrefType "journal-article" @default.
- W2901280873 hasAuthorship W2901280873A5000645986 @default.
- W2901280873 hasAuthorship W2901280873A5010840699 @default.
- W2901280873 hasAuthorship W2901280873A5027835055 @default.
- W2901280873 hasAuthorship W2901280873A5029196561 @default.
- W2901280873 hasAuthorship W2901280873A5029323907 @default.
- W2901280873 hasAuthorship W2901280873A5034051890 @default.
- W2901280873 hasAuthorship W2901280873A5044668501 @default.
- W2901280873 hasAuthorship W2901280873A5071037763 @default.
- W2901280873 hasAuthorship W2901280873A5079330223 @default.
- W2901280873 hasAuthorship W2901280873A5085618254 @default.
- W2901280873 hasAuthorship W2901280873A5087515662 @default.
- W2901280873 hasBestOaLocation W29012808732 @default.
- W2901280873 hasConcept C104317684 @default.
- W2901280873 hasConcept C161624437 @default.
- W2901280873 hasConcept C178666793 @default.
- W2901280873 hasConcept C181199279 @default.
- W2901280873 hasConcept C185592680 @default.
- W2901280873 hasConcept C25824698 @default.
- W2901280873 hasConcept C2776131300 @default.
- W2901280873 hasConcept C2776165026 @default.
- W2901280873 hasConcept C2777658100 @default.
- W2901280873 hasConcept C2781187634 @default.
- W2901280873 hasConcept C2994587330 @default.
- W2901280873 hasConcept C31734879 @default.
- W2901280873 hasConcept C501734568 @default.
- W2901280873 hasConcept C502942594 @default.