Matches in SemOpenAlex for { <https://semopenalex.org/work/W4287462021> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W4287462021 endingPage "5387" @default.
- W4287462021 startingPage "5374" @default.
- W4287462021 abstract "Endometrial cancer (EC) is a highly obesity-driven cancer, with limited treatment options. ONC201 is an imipridone that selectively antagonizes the G protein-coupled receptors dopamine receptor D2 and D3 (DRD2/3) and activates human mitochondrial caseinolytic protease P (ClpP). It is a promising first-in-class small molecule that has been reported to have anti-neoplastic activity in various types of cancer through induction of the integrated stress response (ISR) as well as through stimulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and subsequent induction of apoptosis. ONC201 is being evaluated in Phase II clinical trials for solid tumors and hematological malignancies, including EC. ONC206 is an analog of ONC201 with nanomolar potency in Phase I clinical trials. This study evaluated the anti-tumor efficacy of ONC206 in EC cell lines and the Lkb1fl/flp53fl/fl genetically engineered mouse model of endometrioid EC. ONC206 revealed greater potency than ONC201 in the inhibition of proliferation in EC cell lines, with IC50 concentration ranges of 0.21-0.32 µM for ONC026 versus 2.14-3.53 µM for ONC201. ONC206 induced cellular stress, apoptosis and cell cycle G1 arrest, accompanied by inhibition of the AKT/mTOR/S6 pathways in EC cells. Diet-induced obesity accelerated tumor growth in Lkb1fl/flp53fl/fl mice. ONC206 inhibited EC tumor size and weight in both obese and lean mice after 4 weeks of treatment. Treatment with ONC206 led to a decrease in expression of Ki67, BCL-XL and phosphorylation of S6, as well as an increase in ClpP in endometrial tumors under both obese and lean conditions. Overall, the pre-clinical efficacy of ONC206 is promising and worthy of further exploration in clinical trials for endometrioid EC." @default.
- W4287462021 created "2022-07-25" @default.
- W4287462021 creator A5006651636 @default.
- W4287462021 creator A5007925500 @default.
- W4287462021 creator A5008547275 @default.
- W4287462021 creator A5016145673 @default.
- W4287462021 creator A5030381261 @default.
- W4287462021 creator A5038121350 @default.
- W4287462021 creator A5046472134 @default.
- W4287462021 creator A5054495230 @default.
- W4287462021 creator A5056800304 @default.
- W4287462021 creator A5058573976 @default.
- W4287462021 creator A5059510906 @default.
- W4287462021 creator A5072359750 @default.
- W4287462021 creator A5074450170 @default.
- W4287462021 creator A5084844090 @default.
- W4287462021 creator A5086938995 @default.
- W4287462021 date "2021-01-01" @default.
- W4287462021 modified "2023-10-15" @default.
- W4287462021 title "Highly potent dopamine receptor D2 antagonist ONC206 demonstrates anti-tumorigenic activity in endometrial cancer." @default.
- W4287462021 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34873466" @default.
- W4287462021 hasPublicationYear "2021" @default.
- W4287462021 type Work @default.
- W4287462021 citedByCount "5" @default.
- W4287462021 countsByYear W42874620212022 @default.
- W4287462021 countsByYear W42874620212023 @default.
- W4287462021 crossrefType "journal-article" @default.
- W4287462021 hasAuthorship W4287462021A5006651636 @default.
- W4287462021 hasAuthorship W4287462021A5007925500 @default.
- W4287462021 hasAuthorship W4287462021A5008547275 @default.
- W4287462021 hasAuthorship W4287462021A5016145673 @default.
- W4287462021 hasAuthorship W4287462021A5030381261 @default.
- W4287462021 hasAuthorship W4287462021A5038121350 @default.
- W4287462021 hasAuthorship W4287462021A5046472134 @default.
- W4287462021 hasAuthorship W4287462021A5054495230 @default.
- W4287462021 hasAuthorship W4287462021A5056800304 @default.
- W4287462021 hasAuthorship W4287462021A5058573976 @default.
- W4287462021 hasAuthorship W4287462021A5059510906 @default.
- W4287462021 hasAuthorship W4287462021A5072359750 @default.
- W4287462021 hasAuthorship W4287462021A5074450170 @default.
- W4287462021 hasAuthorship W4287462021A5084844090 @default.
- W4287462021 hasAuthorship W4287462021A5086938995 @default.
- W4287462021 hasConcept C105696609 @default.
- W4287462021 hasConcept C121608353 @default.
- W4287462021 hasConcept C126322002 @default.
- W4287462021 hasConcept C134018914 @default.
- W4287462021 hasConcept C170493617 @default.
- W4287462021 hasConcept C185592680 @default.
- W4287462021 hasConcept C190283241 @default.
- W4287462021 hasConcept C2777088508 @default.
- W4287462021 hasConcept C29537977 @default.
- W4287462021 hasConcept C502942594 @default.
- W4287462021 hasConcept C55493867 @default.
- W4287462021 hasConcept C62112901 @default.
- W4287462021 hasConcept C71924100 @default.
- W4287462021 hasConcept C75217442 @default.
- W4287462021 hasConcept C86554907 @default.
- W4287462021 hasConcept C86803240 @default.
- W4287462021 hasConcept C98274493 @default.
- W4287462021 hasConceptScore W4287462021C105696609 @default.
- W4287462021 hasConceptScore W4287462021C121608353 @default.
- W4287462021 hasConceptScore W4287462021C126322002 @default.
- W4287462021 hasConceptScore W4287462021C134018914 @default.
- W4287462021 hasConceptScore W4287462021C170493617 @default.
- W4287462021 hasConceptScore W4287462021C185592680 @default.
- W4287462021 hasConceptScore W4287462021C190283241 @default.
- W4287462021 hasConceptScore W4287462021C2777088508 @default.
- W4287462021 hasConceptScore W4287462021C29537977 @default.
- W4287462021 hasConceptScore W4287462021C502942594 @default.
- W4287462021 hasConceptScore W4287462021C55493867 @default.
- W4287462021 hasConceptScore W4287462021C62112901 @default.
- W4287462021 hasConceptScore W4287462021C71924100 @default.
- W4287462021 hasConceptScore W4287462021C75217442 @default.
- W4287462021 hasConceptScore W4287462021C86554907 @default.
- W4287462021 hasConceptScore W4287462021C86803240 @default.
- W4287462021 hasConceptScore W4287462021C98274493 @default.
- W4287462021 hasIssue "11" @default.
- W4287462021 hasLocation W42874620211 @default.
- W4287462021 hasOpenAccess W4287462021 @default.
- W4287462021 hasPrimaryLocation W42874620211 @default.
- W4287462021 hasRelatedWork W13120347 @default.
- W4287462021 hasRelatedWork W13227596 @default.
- W4287462021 hasRelatedWork W1435720 @default.
- W4287462021 hasRelatedWork W14437152 @default.
- W4287462021 hasRelatedWork W15425908 @default.
- W4287462021 hasRelatedWork W16098344 @default.
- W4287462021 hasRelatedWork W4952422 @default.
- W4287462021 hasRelatedWork W6766187 @default.
- W4287462021 hasRelatedWork W9873545 @default.
- W4287462021 hasRelatedWork W8423774 @default.
- W4287462021 hasVolume "11" @default.
- W4287462021 isParatext "false" @default.
- W4287462021 isRetracted "false" @default.
- W4287462021 workType "article" @default.