Matches in SemOpenAlex for { <https://semopenalex.org/work/W4362479055> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W4362479055 abstract "<div>Abstract<p>Dysregulation of the PI3K/mTOR pathway, either through amplifications, deletions, or as a direct result of mutations, has been closely linked to the development and progression of a wide range of cancers. Moreover, this pathway activation is a poor prognostic marker for many tumor types and confers resistance to various cancer therapies. Here, we describe VS-5584, a novel, low-molecular weight compound with equivalent potent activity against mTOR (IC<sub>50</sub> = 37 nmol/L) and all class I phosphoinositide 3-kinase (PI3K) isoforms IC<sub>50</sub>: PI3Kα = 16 nmol/L; PI3Kβ = 68 nmol/L; PI3Kγ = 25 nmol/L; PI3Kδ = 42 nmol/L, without relevant activity on 400 lipid and protein kinases. VS-5584 shows robust modulation of cellular PI3K/mTOR pathways, inhibiting phosphorylation of substrates downstream of PI3K and mTORC1/2. A large human cancer cell line panel screen (436 lines) revealed broad antiproliferative sensitivity and that cells harboring mutations in PI3KCA are generally more sensitive toward VS-5584 treatment. VS-5584 exhibits favorable pharmacokinetic properties after oral dosing in mice and is well tolerated. VS-5584 induces long-lasting and dose-dependent inhibition of PI3K/mTOR signaling in tumor tissue, leading to tumor growth inhibition in various rapalog-sensitive and -resistant human xenograft models. Furthermore, VS-5584 is synergistic with an EGF receptor inhibitor in a gastric tumor model. The unique selectivity profile and favorable pharmacologic and pharmaceutical properties of VS-5584 and its efficacy in a wide range of human tumor models supports further investigations of VS-5584 in clinical trials. <i>Mol Cancer Ther; 12(2); 151–61. ©2012 AACR</i>.</p></div>" @default.
- W4362479055 created "2023-04-05" @default.
- W4362479055 creator A5011210921 @default.
- W4362479055 creator A5011353001 @default.
- W4362479055 creator A5037453050 @default.
- W4362479055 creator A5043184297 @default.
- W4362479055 creator A5046719510 @default.
- W4362479055 creator A5049693819 @default.
- W4362479055 creator A5052830654 @default.
- W4362479055 creator A5060539995 @default.
- W4362479055 creator A5060699951 @default.
- W4362479055 creator A5066282840 @default.
- W4362479055 creator A5066743008 @default.
- W4362479055 creator A5068121579 @default.
- W4362479055 creator A5069163925 @default.
- W4362479055 creator A5071846200 @default.
- W4362479055 creator A5072925151 @default.
- W4362479055 creator A5073678842 @default.
- W4362479055 creator A5076145300 @default.
- W4362479055 creator A5080415325 @default.
- W4362479055 creator A5081388884 @default.
- W4362479055 creator A5083376163 @default.
- W4362479055 creator A5085472676 @default.
- W4362479055 creator A5089942407 @default.
- W4362479055 date "2023-04-03" @default.
- W4362479055 modified "2023-09-29" @default.
- W4362479055 title "Data from VS-5584, a Novel and Highly Selective PI3K/mTOR Kinase Inhibitor for the Treatment of Cancer" @default.
- W4362479055 doi "https://doi.org/10.1158/1535-7163.c.6535609" @default.
- W4362479055 hasPublicationYear "2023" @default.
- W4362479055 type Work @default.
- W4362479055 citedByCount "0" @default.
- W4362479055 crossrefType "posted-content" @default.
- W4362479055 hasAuthorship W4362479055A5011210921 @default.
- W4362479055 hasAuthorship W4362479055A5011353001 @default.
- W4362479055 hasAuthorship W4362479055A5037453050 @default.
- W4362479055 hasAuthorship W4362479055A5043184297 @default.
- W4362479055 hasAuthorship W4362479055A5046719510 @default.
- W4362479055 hasAuthorship W4362479055A5049693819 @default.
- W4362479055 hasAuthorship W4362479055A5052830654 @default.
- W4362479055 hasAuthorship W4362479055A5060539995 @default.
- W4362479055 hasAuthorship W4362479055A5060699951 @default.
- W4362479055 hasAuthorship W4362479055A5066282840 @default.
- W4362479055 hasAuthorship W4362479055A5066743008 @default.
- W4362479055 hasAuthorship W4362479055A5068121579 @default.
- W4362479055 hasAuthorship W4362479055A5069163925 @default.
- W4362479055 hasAuthorship W4362479055A5071846200 @default.
- W4362479055 hasAuthorship W4362479055A5072925151 @default.
- W4362479055 hasAuthorship W4362479055A5073678842 @default.
- W4362479055 hasAuthorship W4362479055A5076145300 @default.
- W4362479055 hasAuthorship W4362479055A5080415325 @default.
- W4362479055 hasAuthorship W4362479055A5081388884 @default.
- W4362479055 hasAuthorship W4362479055A5083376163 @default.
- W4362479055 hasAuthorship W4362479055A5085472676 @default.
- W4362479055 hasAuthorship W4362479055A5089942407 @default.
- W4362479055 hasBestOaLocation W43624790552 @default.
- W4362479055 hasConcept C153911025 @default.
- W4362479055 hasConcept C183713625 @default.
- W4362479055 hasConcept C184235292 @default.
- W4362479055 hasConcept C185592680 @default.
- W4362479055 hasConcept C502942594 @default.
- W4362479055 hasConcept C55493867 @default.
- W4362479055 hasConcept C62112901 @default.
- W4362479055 hasConcept C62478195 @default.
- W4362479055 hasConcept C86554907 @default.
- W4362479055 hasConcept C86803240 @default.
- W4362479055 hasConcept C98274493 @default.
- W4362479055 hasConcept C98490376 @default.
- W4362479055 hasConceptScore W4362479055C153911025 @default.
- W4362479055 hasConceptScore W4362479055C183713625 @default.
- W4362479055 hasConceptScore W4362479055C184235292 @default.
- W4362479055 hasConceptScore W4362479055C185592680 @default.
- W4362479055 hasConceptScore W4362479055C502942594 @default.
- W4362479055 hasConceptScore W4362479055C55493867 @default.
- W4362479055 hasConceptScore W4362479055C62112901 @default.
- W4362479055 hasConceptScore W4362479055C62478195 @default.
- W4362479055 hasConceptScore W4362479055C86554907 @default.
- W4362479055 hasConceptScore W4362479055C86803240 @default.
- W4362479055 hasConceptScore W4362479055C98274493 @default.
- W4362479055 hasConceptScore W4362479055C98490376 @default.
- W4362479055 hasLocation W43624790551 @default.
- W4362479055 hasLocation W43624790552 @default.
- W4362479055 hasOpenAccess W4362479055 @default.
- W4362479055 hasPrimaryLocation W43624790551 @default.
- W4362479055 hasRelatedWork W2101083009 @default.
- W4362479055 hasRelatedWork W2334655995 @default.
- W4362479055 hasRelatedWork W2470392790 @default.
- W4362479055 hasRelatedWork W2517175971 @default.
- W4362479055 hasRelatedWork W2617848394 @default.
- W4362479055 hasRelatedWork W2793900392 @default.
- W4362479055 hasRelatedWork W2810995579 @default.
- W4362479055 hasRelatedWork W2958505263 @default.
- W4362479055 hasRelatedWork W2976420392 @default.
- W4362479055 hasRelatedWork W4379618821 @default.
- W4362479055 isParatext "false" @default.
- W4362479055 isRetracted "false" @default.
- W4362479055 workType "article" @default.