FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2116780606> ?p ?o ?g. }

• W2116780606 endingPage "3099" @default.
• W2116780606 startingPage "3090" @default.
• W2116780606 abstract "Abstract Purpose: GDC-0973 is a potent and selective mitogen-activated protein (MAP)/extracellular signal–regulated kinase (ERK) kinase (MEK) inhibitor. Pharmacokinetic–pharmacodynamic (PK–PD) modeling was used to relate GDC-0973 plasma and tumor concentrations, tumor pharmacodynamics and antitumor efficacy to establish pharmacokinetic endpoints and predict active doses in the clinic. Experimental Design: A PK–PD model was used to characterize GDC-0973 tumor disposition and in vivo potency in WM-266-4 xenograft mice. Simulations were conducted using the PK–PD model along with human pharmacokinetics to identify a target plasma concentration and predict active doses. In vivo potency and antitumor efficacy were characterized in A375 melanoma xenograft mice, and a population-based integrated PK–PD-efficacy model was used to relate tumor pharmacodynamics (%pERK decrease) to antitumor activity. Results: GDC-0973 showed a sustained tumor pharmacodynamic response due to longer residence in tumor than in plasma. Following single doses of GDC-0973, estimated in vivo IC50 values of %pERK decrease based on tumor concentrations in xenograft mice were 0.78 (WM-266-4) and 0.52 μmol/L (A375). Following multiple doses of GDC-0973, the estimated in vivo IC50 value in WM-266-4 increased (3.89 μmol/L). Human simulations predicted a minimum target plasma concentration of 83 nmol/L and an active dose range of 28 to 112 mg. The steep relationship between tumor pharmacodynamics (%pERK decrease) and antitumor efficacy suggests a pathway modulation threshold beyond which antitumor efficacy switches on. Conclusions: Clinical observations of %pERK decrease and antitumor activity were consistent with model predictions. This article illustrates how PK–PD modeling can improve the translation of preclinical data to humans by providing a means to integrate preclinical and early clinical data. Clin Cancer Res; 18(11); 3090–9. ©2012 AACR." @default.
• W2116780606 created "2016-06-24" @default.
• W2116780606 creator A5005105589 @default.
• W2116780606 creator A5006218365 @default.
• W2116780606 creator A5010351175 @default.
• W2116780606 creator A5010844468 @default.
• W2116780606 creator A5027133464 @default.
• W2116780606 creator A5027966349 @default.
• W2116780606 creator A5030527565 @default.
• W2116780606 creator A5036398076 @default.
• W2116780606 creator A5037339262 @default.
• W2116780606 creator A5038190062 @default.
• W2116780606 creator A5047135025 @default.
• W2116780606 creator A5048550614 @default.
• W2116780606 creator A5056696568 @default.
• W2116780606 creator A5067029517 @default.
• W2116780606 creator A5075460094 @default.
• W2116780606 creator A5076876084 @default.
• W2116780606 creator A5085236874 @default.
• W2116780606 date "2012-05-31" @default.
• W2116780606 modified "2023-10-17" @default.
• W2116780606 title "Bridging the Gap between Preclinical and Clinical Studies Using Pharmacokinetic–Pharmacodynamic Modeling: An Analysis of GDC-0973, a MEK Inhibitor" @default.
• W2116780606 cites W1593844282 @default.
• W2116780606 cites W159782486 @default.
• W2116780606 cites W1864827749 @default.
• W2116780606 cites W1913521652 @default.
• W2116780606 cites W1970039331 @default.
• W2116780606 cites W1971947883 @default.
• W2116780606 cites W1974091059 @default.
• W2116780606 cites W1985663930 @default.
• W2116780606 cites W1990376228 @default.
• W2116780606 cites W2009642188 @default.
• W2116780606 cites W2028435743 @default.
• W2116780606 cites W2041098455 @default.
• W2116780606 cites W2070658593 @default.
• W2116780606 cites W2080686146 @default.
• W2116780606 cites W2096046981 @default.
• W2116780606 cites W2106543129 @default.
• W2116780606 cites W2107065429 @default.
• W2116780606 cites W2108517627 @default.
• W2116780606 cites W2115629214 @default.
• W2116780606 cites W2124662474 @default.
• W2116780606 cites W2142859055 @default.
• W2116780606 cites W2144169031 @default.
• W2116780606 cites W2150515509 @default.
• W2116780606 cites W2156509877 @default.
• W2116780606 cites W2160363302 @default.
• W2116780606 cites W2161837270 @default.
• W2116780606 cites W2163188200 @default.
• W2116780606 cites W2165280661 @default.
• W2116780606 cites W4377077308 @default.
• W2116780606 doi "https://doi.org/10.1158/1078-0432.ccr-12-0445" @default.
• W2116780606 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22496205" @default.
• W2116780606 hasPublicationYear "2012" @default.
• W2116780606 type Work @default.
• W2116780606 sameAs 2116780606 @default.
• W2116780606 citedByCount "68" @default.
• W2116780606 countsByYear W21167806062012 @default.
• W2116780606 countsByYear W21167806062013 @default.
• W2116780606 countsByYear W21167806062014 @default.
• W2116780606 countsByYear W21167806062015 @default.
• W2116780606 countsByYear W21167806062016 @default.
• W2116780606 countsByYear W21167806062017 @default.
• W2116780606 countsByYear W21167806062018 @default.
• W2116780606 countsByYear W21167806062019 @default.
• W2116780606 countsByYear W21167806062020 @default.
• W2116780606 countsByYear W21167806062021 @default.
• W2116780606 countsByYear W21167806062022 @default.
• W2116780606 countsByYear W21167806062023 @default.
• W2116780606 crossrefType "journal-article" @default.
• W2116780606 hasAuthorship W2116780606A5005105589 @default.
• W2116780606 hasAuthorship W2116780606A5006218365 @default.
• W2116780606 hasAuthorship W2116780606A5010351175 @default.
• W2116780606 hasAuthorship W2116780606A5010844468 @default.
• W2116780606 hasAuthorship W2116780606A5027133464 @default.
• W2116780606 hasAuthorship W2116780606A5027966349 @default.
• W2116780606 hasAuthorship W2116780606A5030527565 @default.
• W2116780606 hasAuthorship W2116780606A5036398076 @default.
• W2116780606 hasAuthorship W2116780606A5037339262 @default.
• W2116780606 hasAuthorship W2116780606A5038190062 @default.
• W2116780606 hasAuthorship W2116780606A5047135025 @default.
• W2116780606 hasAuthorship W2116780606A5048550614 @default.
• W2116780606 hasAuthorship W2116780606A5056696568 @default.
• W2116780606 hasAuthorship W2116780606A5067029517 @default.
• W2116780606 hasAuthorship W2116780606A5075460094 @default.
• W2116780606 hasAuthorship W2116780606A5076876084 @default.
• W2116780606 hasAuthorship W2116780606A5085236874 @default.
• W2116780606 hasBestOaLocation W21167806062 @default.
• W2116780606 hasConcept C111113717 @default.
• W2116780606 hasConcept C112705442 @default.
• W2116780606 hasConcept C126322002 @default.
• W2116780606 hasConcept C150903083 @default.
• W2116780606 hasConcept C184235292 @default.
• W2116780606 hasConcept C185592680 @default.
• W2116780606 hasConcept C202751555 @default.
• W2116780606 hasConcept C207001950 @default.
• W2116780606 hasConcept C2781249067 @default.
• W2116780606 hasConcept C2908647359 @default.

• next