FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2068039003> ?p ?o ?g. }

• W2068039003 endingPage "25" @default.
• W2068039003 startingPage "16" @default.
• W2068039003 abstract "Protein kinase C (PKC) family members such as PKCβII may become activated in the hyperglycemic state associated with diabetes. Preclinical and clinical data implicate aberrant PKC activity in the development of diabetic microvasculature abnormalities. Based on this potential etiological role for PKC in diabetic complications, several therapeutic PKC inhibitors have been investigated in clinical trials for the treatment of diabetic patients. In this report, we present the discovery and preclinical evaluation of a novel class of 3-amino-pyrrolo[3,4-c]pyrazole derivatives as inhibitors of PKC that are structurally distinct from the prototypical indolocarbazole and bisindolylmaleimide PKC inhibitors. From this pyrrolo-pyrazole series, several compounds were identified from biochemical assays as potent, ATP-competitive inhibitors of PKC activity with high specificity for PKC over other protein kinases. These compounds were also found to block PKC signaling activity in multiple cellular functional assays. PF-04577806, a representative from this series, inhibited PKC activity in retinal lysates from diabetic rats stimulated with phorbol myristate acetate. When orally administered, PF-04577806 showed good exposure in the retina of diabetic Long-Evans rats and ameliorated retinal vascular leakage in a streptozotocin-induced diabetic rat model. These novel PKC inhibitors represent a promising new class of targeted protein kinase inhibitors with potential as therapeutic agents for the treatment of patients with diabetic microvascular complications." @default.
• W2068039003 created "2016-06-24" @default.
• W2068039003 creator A5012759062 @default.
• W2068039003 creator A5019731442 @default.
• W2068039003 creator A5021056727 @default.
• W2068039003 creator A5021081344 @default.
• W2068039003 creator A5024505411 @default.
• W2068039003 creator A5029035458 @default.
• W2068039003 creator A5031861539 @default.
• W2068039003 creator A5035042950 @default.
• W2068039003 creator A5035849441 @default.
• W2068039003 creator A5046375198 @default.
• W2068039003 creator A5049279899 @default.
• W2068039003 creator A5058759123 @default.
• W2068039003 creator A5063127492 @default.
• W2068039003 creator A5063396555 @default.
• W2068039003 creator A5064787088 @default.
• W2068039003 creator A5065859286 @default.
• W2068039003 creator A5070775386 @default.
• W2068039003 creator A5084583076 @default.
• W2068039003 creator A5085318164 @default.
• W2068039003 creator A5091860060 @default.
• W2068039003 date "2010-02-01" @default.
• W2068039003 modified "2023-09-27" @default.
• W2068039003 title "Discovery of a novel class of targeted kinase inhibitors that blocks protein kinase C signaling and ameliorates retinal vascular leakage in a diabetic rat model" @default.
• W2068039003 cites W1605140126 @default.
• W2068039003 cites W1641731911 @default.
• W2068039003 cites W1755902553 @default.
• W2068039003 cites W1958359496 @default.
• W2068039003 cites W1964603185 @default.
• W2068039003 cites W1966419887 @default.
• W2068039003 cites W1985242446 @default.
• W2068039003 cites W1992451339 @default.
• W2068039003 cites W1997851369 @default.
• W2068039003 cites W1997926000 @default.
• W2068039003 cites W2001030939 @default.
• W2068039003 cites W2001097406 @default.
• W2068039003 cites W2009982210 @default.
• W2068039003 cites W2014582878 @default.
• W2068039003 cites W2015080165 @default.
• W2068039003 cites W2020185097 @default.
• W2068039003 cites W2021759592 @default.
• W2068039003 cites W2025732390 @default.
• W2068039003 cites W2034460590 @default.
• W2068039003 cites W2034874989 @default.
• W2068039003 cites W2038040871 @default.
• W2068039003 cites W2039617541 @default.
• W2068039003 cites W2047094134 @default.
• W2068039003 cites W2050537958 @default.
• W2068039003 cites W2050629960 @default.
• W2068039003 cites W2052750950 @default.
• W2068039003 cites W2075898803 @default.
• W2068039003 cites W2078308664 @default.
• W2068039003 cites W2084691395 @default.
• W2068039003 cites W2084823433 @default.
• W2068039003 cites W2095724500 @default.
• W2068039003 cites W2095745765 @default.
• W2068039003 cites W2098316409 @default.
• W2068039003 cites W2100772783 @default.
• W2068039003 cites W2103370047 @default.
• W2068039003 cites W2103761135 @default.
• W2068039003 cites W2117029515 @default.
• W2068039003 cites W2125294721 @default.
• W2068039003 cites W2130147203 @default.
• W2068039003 cites W2136284645 @default.
• W2068039003 cites W2142730314 @default.
• W2068039003 cites W2143287170 @default.
• W2068039003 cites W2158722505 @default.
• W2068039003 cites W2159337738 @default.
• W2068039003 cites W2162543333 @default.
• W2068039003 cites W2591764924 @default.
• W2068039003 doi "https://doi.org/10.1016/j.ejphar.2009.10.029" @default.
• W2068039003 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19850035" @default.
• W2068039003 hasPublicationYear "2010" @default.
• W2068039003 type Work @default.
• W2068039003 sameAs 2068039003 @default.
• W2068039003 citedByCount "10" @default.
• W2068039003 countsByYear W20680390032012 @default.
• W2068039003 countsByYear W20680390032013 @default.
• W2068039003 countsByYear W20680390032014 @default.
• W2068039003 countsByYear W20680390032015 @default.
• W2068039003 countsByYear W20680390032019 @default.
• W2068039003 crossrefType "journal-article" @default.
• W2068039003 hasAuthorship W2068039003A5012759062 @default.
• W2068039003 hasAuthorship W2068039003A5019731442 @default.
• W2068039003 hasAuthorship W2068039003A5021056727 @default.
• W2068039003 hasAuthorship W2068039003A5021081344 @default.
• W2068039003 hasAuthorship W2068039003A5024505411 @default.
• W2068039003 hasAuthorship W2068039003A5029035458 @default.
• W2068039003 hasAuthorship W2068039003A5031861539 @default.
• W2068039003 hasAuthorship W2068039003A5035042950 @default.
• W2068039003 hasAuthorship W2068039003A5035849441 @default.
• W2068039003 hasAuthorship W2068039003A5046375198 @default.
• W2068039003 hasAuthorship W2068039003A5049279899 @default.
• W2068039003 hasAuthorship W2068039003A5058759123 @default.
• W2068039003 hasAuthorship W2068039003A5063127492 @default.
• W2068039003 hasAuthorship W2068039003A5063396555 @default.
• W2068039003 hasAuthorship W2068039003A5064787088 @default.

• next