Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361243411> ?p ?o ?g. }
Showing items 1 to 100 of
100
with 100 items per page.
- W4361243411 abstract "<div>Abstract<p>The mammalian target of rapamycin (mTOR) kinase forms two multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, cell survival, and autophagy. Allosteric inhibitors of mTORC1, such as rapamycin, have been extensively used to study tumor cell growth, proliferation, and autophagy but have shown only limited clinical utility. Here, we describe AZD8055, a novel ATP-competitive inhibitor of mTOR kinase activity, with an IC<sub>50</sub> of 0.8 nmol/L. AZD8055 showed excellent selectivity (∼1,000-fold) against all class I phosphatidylinositol 3-kinase (PI3K) isoforms and other members of the PI3K-like kinase family. Furthermore, there was no significant activity against a panel of 260 kinases at concentrations up to 10 μmol/L. AZD8055 inhibits the phosphorylation of mTORC1 substrates p70S6K and 4E-BP1 as well as phosphorylation of the mTORC2 substrate AKT and downstream proteins. The rapamycin-resistant T37/46 phosphorylation sites on 4E-BP1 were fully inhibited by AZD8055, resulting in significant inhibition of cap-dependent translation. <i>In vitro</i>, AZD8055 potently inhibits proliferation and induces autophagy in H838 and A549 cells. <i>In vivo</i>, AZD8055 induces a dose-dependent pharmacodynamic effect on phosphorylated S6 and phosphorylated AKT at plasma concentrations leading to tumor growth inhibition. Notably, AZD8055 results in significant growth inhibition and/or regression in xenografts, representing a broad range of human tumor types. AZD8055 is currently in phase I clinical trials. Cancer Res; 70(1); 288–98</p></div>" @default.
- W4361243411 created "2023-03-31" @default.
- W4361243411 creator A5000275517 @default.
- W4361243411 creator A5003346389 @default.
- W4361243411 creator A5011521400 @default.
- W4361243411 creator A5012988279 @default.
- W4361243411 creator A5013730565 @default.
- W4361243411 creator A5014622191 @default.
- W4361243411 creator A5017227434 @default.
- W4361243411 creator A5027804793 @default.
- W4361243411 creator A5028178595 @default.
- W4361243411 creator A5039494440 @default.
- W4361243411 creator A5040373927 @default.
- W4361243411 creator A5051322178 @default.
- W4361243411 creator A5055901141 @default.
- W4361243411 creator A5056706417 @default.
- W4361243411 creator A5057710096 @default.
- W4361243411 creator A5059693322 @default.
- W4361243411 creator A5063506272 @default.
- W4361243411 creator A5067097626 @default.
- W4361243411 creator A5080782403 @default.
- W4361243411 creator A5081302297 @default.
- W4361243411 creator A5084206386 @default.
- W4361243411 creator A5085921889 @default.
- W4361243411 creator A5088107386 @default.
- W4361243411 creator A5091433786 @default.
- W4361243411 date "2023-03-30" @default.
- W4361243411 modified "2023-09-29" @default.
- W4361243411 title "Data from AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with <i>In vitro</i> and <i>In vivo</i> Antitumor Activity" @default.
- W4361243411 doi "https://doi.org/10.1158/0008-5472.c.6500190.v1" @default.
- W4361243411 hasPublicationYear "2023" @default.
- W4361243411 type Work @default.
- W4361243411 citedByCount "0" @default.
- W4361243411 crossrefType "posted-content" @default.
- W4361243411 hasAuthorship W4361243411A5000275517 @default.
- W4361243411 hasAuthorship W4361243411A5003346389 @default.
- W4361243411 hasAuthorship W4361243411A5011521400 @default.
- W4361243411 hasAuthorship W4361243411A5012988279 @default.
- W4361243411 hasAuthorship W4361243411A5013730565 @default.
- W4361243411 hasAuthorship W4361243411A5014622191 @default.
- W4361243411 hasAuthorship W4361243411A5017227434 @default.
- W4361243411 hasAuthorship W4361243411A5027804793 @default.
- W4361243411 hasAuthorship W4361243411A5028178595 @default.
- W4361243411 hasAuthorship W4361243411A5039494440 @default.
- W4361243411 hasAuthorship W4361243411A5040373927 @default.
- W4361243411 hasAuthorship W4361243411A5051322178 @default.
- W4361243411 hasAuthorship W4361243411A5055901141 @default.
- W4361243411 hasAuthorship W4361243411A5056706417 @default.
- W4361243411 hasAuthorship W4361243411A5057710096 @default.
- W4361243411 hasAuthorship W4361243411A5059693322 @default.
- W4361243411 hasAuthorship W4361243411A5063506272 @default.
- W4361243411 hasAuthorship W4361243411A5067097626 @default.
- W4361243411 hasAuthorship W4361243411A5080782403 @default.
- W4361243411 hasAuthorship W4361243411A5081302297 @default.
- W4361243411 hasAuthorship W4361243411A5084206386 @default.
- W4361243411 hasAuthorship W4361243411A5085921889 @default.
- W4361243411 hasAuthorship W4361243411A5088107386 @default.
- W4361243411 hasAuthorship W4361243411A5091433786 @default.
- W4361243411 hasBestOaLocation W43612434112 @default.
- W4361243411 hasConcept C107846503 @default.
- W4361243411 hasConcept C11960822 @default.
- W4361243411 hasConcept C184235292 @default.
- W4361243411 hasConcept C2777949483 @default.
- W4361243411 hasConcept C55493867 @default.
- W4361243411 hasConcept C62112901 @default.
- W4361243411 hasConcept C62478195 @default.
- W4361243411 hasConcept C75217442 @default.
- W4361243411 hasConcept C86554907 @default.
- W4361243411 hasConcept C86803240 @default.
- W4361243411 hasConcept C98274493 @default.
- W4361243411 hasConcept C98490376 @default.
- W4361243411 hasConceptScore W4361243411C107846503 @default.
- W4361243411 hasConceptScore W4361243411C11960822 @default.
- W4361243411 hasConceptScore W4361243411C184235292 @default.
- W4361243411 hasConceptScore W4361243411C2777949483 @default.
- W4361243411 hasConceptScore W4361243411C55493867 @default.
- W4361243411 hasConceptScore W4361243411C62112901 @default.
- W4361243411 hasConceptScore W4361243411C62478195 @default.
- W4361243411 hasConceptScore W4361243411C75217442 @default.
- W4361243411 hasConceptScore W4361243411C86554907 @default.
- W4361243411 hasConceptScore W4361243411C86803240 @default.
- W4361243411 hasConceptScore W4361243411C98274493 @default.
- W4361243411 hasConceptScore W4361243411C98490376 @default.
- W4361243411 hasLocation W43612434111 @default.
- W4361243411 hasLocation W43612434112 @default.
- W4361243411 hasOpenAccess W4361243411 @default.
- W4361243411 hasPrimaryLocation W43612434111 @default.
- W4361243411 hasRelatedWork W1966019502 @default.
- W4361243411 hasRelatedWork W1983698019 @default.
- W4361243411 hasRelatedWork W2016514257 @default.
- W4361243411 hasRelatedWork W2026423184 @default.
- W4361243411 hasRelatedWork W2135012769 @default.
- W4361243411 hasRelatedWork W2154572127 @default.
- W4361243411 hasRelatedWork W2287822496 @default.
- W4361243411 hasRelatedWork W2499779639 @default.
- W4361243411 hasRelatedWork W2744183625 @default.
- W4361243411 hasRelatedWork W4225422229 @default.
- W4361243411 isParatext "false" @default.
- W4361243411 isRetracted "false" @default.
- W4361243411 workType "article" @default.