FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386996831> ?p ?o ?g. }

• W4386996831 endingPage "2371" @default.
• W4386996831 startingPage "2371" @default.
• W4386996831 abstract "Glioblastoma is one of the most common and aggressive forms of brain tumor, a rare disease for which there is a great need for innovative therapies. ONC201, a new drug substance, has been used in a compassionate treatment program where the choice of dosage form and regimen have yet to be justified. The prior knowledge needed to anticipate ONC201 stability problems has recently been partially addressed, by (i) showing that ONC201 is sensitive to light and oxidation and (ii) identifying the molecular structures of the main degradation products formed. The aim of the work presented here was to improve our understanding of the degradation pathways of ONC201 using data from ab initio calculations and experimental work to supplement the structural information we already published. The C–H bonds located αto the amine of the tetrahydropyridine group and those located alpha to the imine function of the dihydroimidazole group exhibit the lowest bond dissociation energies (BDEs) within the ONC201 molecule. Moreover, these values drop well below 90 kcal.mol−1 when ONC201 is in an excited state (S1; T1). The structures of the photoproducts we had previously identified are consistent with these data, showing that they would have resulted from radical processes following the abstraction of alpha hydrogens. Concerning ONC201’s sensitivity to oxidation, the structures of the oxidation products matched the critical points revealed through mapped electrostatic potential (MEP) and average local ionization energy (ALIE). The data obtained from ab initio calculations and experimental work showed that the reactivity of ONC201 to light and oxidation conditions is highly dependent on pH. While an acidic environment (pH < 6) contributes to making ONC201 quantitatively more stable in solution in the face of oxidation and photo-oxidation, it nevertheless seems that certain chemical groups in the molecule are more exposed to nucleophilic attacks, which explains the variation observed in the profile of degradation products formed in the presence of certain antioxidants tested. This information is crucial to better understand the stability results in the presence of antioxidant agents and to determine the right conditions for them to act." @default.
• W4386996831 created "2023-09-25" @default.
• W4386996831 creator A5024089310 @default.
• W4386996831 creator A5028589644 @default.
• W4386996831 creator A5048911676 @default.
• W4386996831 creator A5054267552 @default.
• W4386996831 creator A5055014867 @default.
• W4386996831 creator A5056855451 @default.
• W4386996831 creator A5066285906 @default.
• W4386996831 creator A5075779028 @default.
• W4386996831 creator A5082214210 @default.
• W4386996831 creator A5091949991 @default.
• W4386996831 date "2023-09-22" @default.
• W4386996831 modified "2023-10-16" @default.
• W4386996831 title "Molecular Mechanisms Involved in the Chemical Instability of ONC201 and Methods to Counter Its Degradation in Solution" @default.
• W4386996831 cites W1983391718 @default.
• W4386996831 cites W2016325409 @default.
• W4386996831 cites W2048447206 @default.
• W4386996831 cites W2065937814 @default.
• W4386996831 cites W2166067630 @default.
• W4386996831 cites W2334379314 @default.
• W4386996831 cites W2529213922 @default.
• W4386996831 cites W2592166782 @default.
• W4386996831 cites W2761284642 @default.
• W4386996831 cites W2764083878 @default.
• W4386996831 cites W2897396242 @default.
• W4386996831 cites W2917823094 @default.
• W4386996831 cites W2947026434 @default.
• W4386996831 cites W2952112377 @default.
• W4386996831 cites W2994794838 @default.
• W4386996831 cites W2997708901 @default.
• W4386996831 cites W3005288840 @default.
• W4386996831 cites W3134793945 @default.
• W4386996831 cites W3163885706 @default.
• W4386996831 cites W4210249219 @default.
• W4386996831 cites W4280608343 @default.
• W4386996831 cites W4319656966 @default.
• W4386996831 cites W4376644096 @default.
• W4386996831 cites W4382199687 @default.
• W4386996831 cites W4382516172 @default.
• W4386996831 doi "https://doi.org/10.3390/pharmaceutics15102371" @default.
• W4386996831 hasPublicationYear "2023" @default.
• W4386996831 type Work @default.
• W4386996831 citedByCount "0" @default.
• W4386996831 crossrefType "journal-article" @default.
• W4386996831 hasAuthorship W4386996831A5024089310 @default.
• W4386996831 hasAuthorship W4386996831A5028589644 @default.
• W4386996831 hasAuthorship W4386996831A5048911676 @default.
• W4386996831 hasAuthorship W4386996831A5054267552 @default.
• W4386996831 hasAuthorship W4386996831A5055014867 @default.
• W4386996831 hasAuthorship W4386996831A5056855451 @default.
• W4386996831 hasAuthorship W4386996831A5066285906 @default.
• W4386996831 hasAuthorship W4386996831A5075779028 @default.
• W4386996831 hasAuthorship W4386996831A5082214210 @default.
• W4386996831 hasAuthorship W4386996831A5091949991 @default.
• W4386996831 hasBestOaLocation W43869968311 @default.
• W4386996831 hasConcept C102931765 @default.
• W4386996831 hasConcept C147597530 @default.
• W4386996831 hasConcept C178790620 @default.
• W4386996831 hasConcept C185592680 @default.
• W4386996831 hasConcept C2781442258 @default.
• W4386996831 hasConcept C62396407 @default.
• W4386996831 hasConceptScore W4386996831C102931765 @default.
• W4386996831 hasConceptScore W4386996831C147597530 @default.
• W4386996831 hasConceptScore W4386996831C178790620 @default.
• W4386996831 hasConceptScore W4386996831C185592680 @default.
• W4386996831 hasConceptScore W4386996831C2781442258 @default.
• W4386996831 hasConceptScore W4386996831C62396407 @default.
• W4386996831 hasIssue "10" @default.
• W4386996831 hasLocation W43869968311 @default.
• W4386996831 hasOpenAccess W4386996831 @default.
• W4386996831 hasPrimaryLocation W43869968311 @default.
• W4386996831 hasRelatedWork W1976260399 @default.
• W4386996831 hasRelatedWork W2004977407 @default.
• W4386996831 hasRelatedWork W2054185339 @default.
• W4386996831 hasRelatedWork W2093856911 @default.
• W4386996831 hasRelatedWork W2127181935 @default.
• W4386996831 hasRelatedWork W2152852609 @default.
• W4386996831 hasRelatedWork W2351206131 @default.
• W4386996831 hasRelatedWork W2951415669 @default.
• W4386996831 hasRelatedWork W4253561093 @default.
• W4386996831 hasRelatedWork W2042613698 @default.
• W4386996831 hasVolume "15" @default.
• W4386996831 isParatext "false" @default.
• W4386996831 isRetracted "false" @default.
• W4386996831 workType "article" @default.