Matches in SemOpenAlex for { <https://semopenalex.org/work/W3047528703> ?p ?o ?g. }
- W3047528703 endingPage "112678" @default.
- W3047528703 startingPage "112678" @default.
- W3047528703 abstract "Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a recently validated therapeutic target for lowering low-density lipoprotein cholesterol (LDL-C). Through phenotypic screening, we previously discovered a class of small-molecules with a 2,3′-diindolymethane (DIM) skeleton that can decrease the expression of PCSK9. But these compounds have low potency and low metabolically stability. After performing structure-activity relationship (SAR) optimization by nitrogen scan, deuterium substitution and fluorine scan, we identified a series of much more potent and metabolically stable PCSK9 modulators. A preliminary in vivo pharmacokinetic study was performed for representative analogues difluorodiindolyketone (DFDIK) 12 and difluorobenzoimidazolylindolylketone (DFBIIK-1) 13. The in vitro metabolic stability correlate well with the in vivo data. The most potent compound 21 has the EC50 of 0.15 nM. Our SAR studies also indicated that the NH on the indole ring of 21 can tolerate more function groups, which may facilitate the mechanism of action studies and also allow further improvement of the pharmacological properties." @default.
- W3047528703 created "2020-08-10" @default.
- W3047528703 creator A5000617179 @default.
- W3047528703 creator A5003503515 @default.
- W3047528703 creator A5010606622 @default.
- W3047528703 creator A5066344931 @default.
- W3047528703 creator A5070030950 @default.
- W3047528703 creator A5071264789 @default.
- W3047528703 creator A5073813004 @default.
- W3047528703 creator A5087354808 @default.
- W3047528703 date "2020-11-01" @default.
- W3047528703 modified "2023-09-26" @default.
- W3047528703 title "From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators" @default.
- W3047528703 cites W1870321215 @default.
- W3047528703 cites W1981066521 @default.
- W3047528703 cites W1983401069 @default.
- W3047528703 cites W1987486422 @default.
- W3047528703 cites W1990187433 @default.
- W3047528703 cites W1990322073 @default.
- W3047528703 cites W1994479681 @default.
- W3047528703 cites W1997212073 @default.
- W3047528703 cites W2001313012 @default.
- W3047528703 cites W2001328643 @default.
- W3047528703 cites W2011857098 @default.
- W3047528703 cites W2022068475 @default.
- W3047528703 cites W2033043158 @default.
- W3047528703 cites W2040612932 @default.
- W3047528703 cites W2047861227 @default.
- W3047528703 cites W2052214665 @default.
- W3047528703 cites W2054610237 @default.
- W3047528703 cites W2060333462 @default.
- W3047528703 cites W2063498224 @default.
- W3047528703 cites W2078669364 @default.
- W3047528703 cites W2087956853 @default.
- W3047528703 cites W2088358411 @default.
- W3047528703 cites W2088786893 @default.
- W3047528703 cites W2097472327 @default.
- W3047528703 cites W2116087305 @default.
- W3047528703 cites W2123059506 @default.
- W3047528703 cites W2127896256 @default.
- W3047528703 cites W2131561840 @default.
- W3047528703 cites W2140310496 @default.
- W3047528703 cites W2158658436 @default.
- W3047528703 cites W2168836317 @default.
- W3047528703 cites W2264719596 @default.
- W3047528703 cites W2290120395 @default.
- W3047528703 cites W2313227787 @default.
- W3047528703 cites W2314067773 @default.
- W3047528703 cites W2315828900 @default.
- W3047528703 cites W2317462866 @default.
- W3047528703 cites W2319505350 @default.
- W3047528703 cites W2333129245 @default.
- W3047528703 cites W2478977955 @default.
- W3047528703 cites W2530737230 @default.
- W3047528703 cites W2555483953 @default.
- W3047528703 cites W2595169180 @default.
- W3047528703 cites W2596179513 @default.
- W3047528703 cites W2729684734 @default.
- W3047528703 cites W2750222245 @default.
- W3047528703 cites W2752803806 @default.
- W3047528703 cites W2786967171 @default.
- W3047528703 cites W2793825078 @default.
- W3047528703 cites W2807585481 @default.
- W3047528703 cites W2890685481 @default.
- W3047528703 cites W2901454264 @default.
- W3047528703 cites W2903215969 @default.
- W3047528703 cites W2909275830 @default.
- W3047528703 cites W2922621730 @default.
- W3047528703 cites W2953074494 @default.
- W3047528703 cites W2955861198 @default.
- W3047528703 cites W2971552905 @default.
- W3047528703 cites W2981983231 @default.
- W3047528703 cites W3001608717 @default.
- W3047528703 cites W3004322307 @default.
- W3047528703 cites W3006188639 @default.
- W3047528703 cites W4233650392 @default.
- W3047528703 doi "https://doi.org/10.1016/j.ejmech.2020.112678" @default.
- W3047528703 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7572704" @default.
- W3047528703 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/32823006" @default.
- W3047528703 hasPublicationYear "2020" @default.
- W3047528703 type Work @default.
- W3047528703 sameAs 3047528703 @default.
- W3047528703 citedByCount "5" @default.
- W3047528703 countsByYear W30475287032021 @default.
- W3047528703 countsByYear W30475287032022 @default.
- W3047528703 countsByYear W30475287032023 @default.
- W3047528703 crossrefType "journal-article" @default.
- W3047528703 hasAuthorship W3047528703A5000617179 @default.
- W3047528703 hasAuthorship W3047528703A5003503515 @default.
- W3047528703 hasAuthorship W3047528703A5010606622 @default.
- W3047528703 hasAuthorship W3047528703A5066344931 @default.
- W3047528703 hasAuthorship W3047528703A5070030950 @default.
- W3047528703 hasAuthorship W3047528703A5071264789 @default.
- W3047528703 hasAuthorship W3047528703A5073813004 @default.
- W3047528703 hasAuthorship W3047528703A5087354808 @default.
- W3047528703 hasBestOaLocation W30475287032 @default.
- W3047528703 hasConcept C150903083 @default.
- W3047528703 hasConcept C181199279 @default.