Matches in SemOpenAlex for { <https://semopenalex.org/work/W3033103661> ?p ?o ?g. }
- W3033103661 endingPage "6846" @default.
- W3033103661 startingPage "6834" @default.
- W3033103661 abstract "Tankyrases 1 and 2 are central biotargets in the WNT/β-catenin signaling and Hippo signaling pathways. We have previously developed tankyrase inhibitors bearing a 1,2,4-triazole moiety and binding predominantly to the adenosine binding site of the tankyrase catalytic domain. Here we describe a systematic structure-guided lead optimization approach of these tankyrase inhibitors. The central 1,2,4-triazole template and trans-cyclobutyl linker of the lead compound 1 were left unchanged, while side-group East, West, and South moieties were altered by introducing different building blocks defined as point mutations. The systematic study provided a novel series of compounds reaching picomolar IC50 inhibition in WNT/β-catenin signaling cellular reporter assay. The novel optimized lead 13 resolves previous atropisomerism, solubility, and Caco-2 efflux liabilities. 13 shows a favorable ADME profile, including improved Caco-2 permeability and oral bioavailability in mice, and exhibits antiproliferative efficacy in the colon cancer cell line COLO 320DM in vitro." @default.
- W3033103661 created "2020-06-12" @default.
- W3033103661 creator A5001857780 @default.
- W3033103661 creator A5009279555 @default.
- W3033103661 creator A5010379244 @default.
- W3033103661 creator A5018343322 @default.
- W3033103661 creator A5034759535 @default.
- W3033103661 creator A5037166494 @default.
- W3033103661 creator A5038563052 @default.
- W3033103661 creator A5049855471 @default.
- W3033103661 creator A5061328925 @default.
- W3033103661 creator A5062886298 @default.
- W3033103661 creator A5064049269 @default.
- W3033103661 creator A5082877213 @default.
- W3033103661 creator A5088271343 @default.
- W3033103661 date "2020-06-08" @default.
- W3033103661 modified "2023-10-15" @default.
- W3033103661 title "Preclinical Lead Optimization of a 1,2,4-Triazole Based Tankyrase Inhibitor" @default.
- W3033103661 cites W1925213563 @default.
- W3033103661 cites W2057257265 @default.
- W3033103661 cites W2061712281 @default.
- W3033103661 cites W2065323053 @default.
- W3033103661 cites W2072493619 @default.
- W3033103661 cites W2101889783 @default.
- W3033103661 cites W2105240743 @default.
- W3033103661 cites W2141505580 @default.
- W3033103661 cites W2144081223 @default.
- W3033103661 cites W2144311146 @default.
- W3033103661 cites W2149987834 @default.
- W3033103661 cites W2159059125 @default.
- W3033103661 cites W2159211495 @default.
- W3033103661 cites W2163341755 @default.
- W3033103661 cites W2176313700 @default.
- W3033103661 cites W2191108627 @default.
- W3033103661 cites W2318878569 @default.
- W3033103661 cites W2332224602 @default.
- W3033103661 cites W2335442430 @default.
- W3033103661 cites W2521785925 @default.
- W3033103661 cites W2566586795 @default.
- W3033103661 cites W2621361823 @default.
- W3033103661 cites W2762375235 @default.
- W3033103661 cites W2765414974 @default.
- W3033103661 cites W2767684755 @default.
- W3033103661 cites W2768843451 @default.
- W3033103661 cites W2771031544 @default.
- W3033103661 cites W2771937306 @default.
- W3033103661 cites W2773532695 @default.
- W3033103661 cites W2782910412 @default.
- W3033103661 cites W2796153225 @default.
- W3033103661 cites W2809572644 @default.
- W3033103661 cites W2890709794 @default.
- W3033103661 cites W2895362354 @default.
- W3033103661 cites W2966142515 @default.
- W3033103661 cites W2975791438 @default.
- W3033103661 cites W3020133834 @default.
- W3033103661 cites W4248872320 @default.
- W3033103661 cites W822602707 @default.
- W3033103661 doi "https://doi.org/10.1021/acs.jmedchem.0c00208" @default.
- W3033103661 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8008393" @default.
- W3033103661 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32511917" @default.
- W3033103661 hasPublicationYear "2020" @default.
- W3033103661 type Work @default.
- W3033103661 sameAs 3033103661 @default.
- W3033103661 citedByCount "25" @default.
- W3033103661 countsByYear W30331036612020 @default.
- W3033103661 countsByYear W30331036612021 @default.
- W3033103661 countsByYear W30331036612022 @default.
- W3033103661 countsByYear W30331036612023 @default.
- W3033103661 crossrefType "journal-article" @default.
- W3033103661 hasAuthorship W3033103661A5001857780 @default.
- W3033103661 hasAuthorship W3033103661A5009279555 @default.
- W3033103661 hasAuthorship W3033103661A5010379244 @default.
- W3033103661 hasAuthorship W3033103661A5018343322 @default.
- W3033103661 hasAuthorship W3033103661A5034759535 @default.
- W3033103661 hasAuthorship W3033103661A5037166494 @default.
- W3033103661 hasAuthorship W3033103661A5038563052 @default.
- W3033103661 hasAuthorship W3033103661A5049855471 @default.
- W3033103661 hasAuthorship W3033103661A5061328925 @default.
- W3033103661 hasAuthorship W3033103661A5062886298 @default.
- W3033103661 hasAuthorship W3033103661A5064049269 @default.
- W3033103661 hasAuthorship W3033103661A5082877213 @default.
- W3033103661 hasAuthorship W3033103661A5088271343 @default.
- W3033103661 hasBestOaLocation W30331036612 @default.
- W3033103661 hasConcept C114793014 @default.
- W3033103661 hasConcept C127313418 @default.
- W3033103661 hasConcept C178790620 @default.
- W3033103661 hasConcept C185592680 @default.
- W3033103661 hasConcept C202751555 @default.
- W3033103661 hasConcept C2777093003 @default.
- W3033103661 hasConcept C2777752112 @default.
- W3033103661 hasConcept C2777907353 @default.
- W3033103661 hasConcept C55493867 @default.
- W3033103661 hasConcept C71924100 @default.
- W3033103661 hasConcept C98274493 @default.
- W3033103661 hasConceptScore W3033103661C114793014 @default.
- W3033103661 hasConceptScore W3033103661C127313418 @default.
- W3033103661 hasConceptScore W3033103661C178790620 @default.
- W3033103661 hasConceptScore W3033103661C185592680 @default.