FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4311165269> ?p ?o ?g. }

• W4311165269 endingPage "263" @default.
• W4311165269 startingPage "254" @default.
• W4311165269 abstract "Abstract Antibody–drug conjugates (ADC) delivering pyrrolobenzodiazepine (PBD) DNA cross-linkers are currently being evaluated in clinical trials, with encouraging results in Hodgkin and non–Hodgkin lymphomas. The first example of an ADC delivering a PBD DNA cross-linker (loncastuximab tesirine) has been recently approved by the FDA for the treatment of relapsed and refractory diffuse large B-cell lymphoma. There has also been considerable interest in mono-alkylating PBD analogs. We conducted a head-to-head comparison of a conventional PBD bis-imine and a novel PBD mono-imine. Key Mitsunobu chemistry allowed clean and convenient access to the mono-imine class. Extensive DNA-binding studies revealed that the mono-imine mediated a type of DNA interaction that is described as “pseudo cross-linking,” as well as alkylation. The PBD mono-imine ADC demonstrated robust antitumor activity in mice bearing human tumor xenografts at doses 3-fold higher than those that were efficacious for the PBD bis-imine ADC. A single-dose toxicology study in rats demonstrated that the MTD of the PBD mono-alkylator ADC was approximately 3-fold higher than that of the ADC bearing a bis-imine payload, suggesting a comparable therapeutic index for this molecule. However, although both ADCs caused myelosuppression, renal toxicity was observed only for the bis-imine, indicating possible differences in toxicologic profiles that could influence tolerability and therapeutic index. These data show that mono-amine PBDs have physicochemical and pharmacotoxicologic properties distinct from their cross-linking analogs and support their potential utility as a novel class of ADC payload." @default.
• W4311165269 created "2022-12-24" @default.
• W4311165269 creator A5000652124 @default.
• W4311165269 creator A5003565644 @default.
• W4311165269 creator A5009598734 @default.
• W4311165269 creator A5012379209 @default.
• W4311165269 creator A5012867126 @default.
• W4311165269 creator A5013463645 @default.
• W4311165269 creator A5021462287 @default.
• W4311165269 creator A5040980936 @default.
• W4311165269 creator A5042410729 @default.
• W4311165269 creator A5043092566 @default.
• W4311165269 creator A5045583717 @default.
• W4311165269 creator A5047010658 @default.
• W4311165269 creator A5048240683 @default.
• W4311165269 creator A5051368970 @default.
• W4311165269 creator A5055669649 @default.
• W4311165269 creator A5063961568 @default.
• W4311165269 creator A5070047090 @default.
• W4311165269 creator A5086415657 @default.
• W4311165269 date "2022-12-02" @default.
• W4311165269 modified "2023-10-17" @default.
• W4311165269 title "Comparison of Pyrrolobenzodiazepine Dimer Bis-imine versus Mono-imine: DNA Interstrand Cross-linking, Cytotoxicity, Antibody–Drug Conjugate Efficacy and Toxicity" @default.
• W4311165269 cites W148147721 @default.
• W4311165269 cites W1822869875 @default.
• W4311165269 cites W2000027123 @default.
• W4311165269 cites W2030249962 @default.
• W4311165269 cites W2031091007 @default.
• W4311165269 cites W2041412977 @default.
• W4311165269 cites W2042106494 @default.
• W4311165269 cites W2082412374 @default.
• W4311165269 cites W2120300441 @default.
• W4311165269 cites W2127373755 @default.
• W4311165269 cites W2137763083 @default.
• W4311165269 cites W2149711103 @default.
• W4311165269 cites W2203423087 @default.
• W4311165269 cites W2233888390 @default.
• W4311165269 cites W2395592928 @default.
• W4311165269 cites W2403458189 @default.
• W4311165269 cites W2465201008 @default.
• W4311165269 cites W2513682949 @default.
• W4311165269 cites W2549780925 @default.
• W4311165269 cites W2560431464 @default.
• W4311165269 cites W2592363471 @default.
• W4311165269 cites W2636487951 @default.
• W4311165269 cites W2790219752 @default.
• W4311165269 cites W2839071055 @default.
• W4311165269 cites W2883952232 @default.
• W4311165269 cites W2886741567 @default.
• W4311165269 cites W2951939015 @default.
• W4311165269 cites W2958762925 @default.
• W4311165269 cites W2965395580 @default.
• W4311165269 cites W2987115036 @default.
• W4311165269 cites W2989674878 @default.
• W4311165269 cites W2991390941 @default.
• W4311165269 cites W3178865470 @default.
• W4311165269 doi "https://doi.org/10.1158/1535-7163.mct-21-0693" @default.
• W4311165269 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36474428" @default.
• W4311165269 hasPublicationYear "2022" @default.
• W4311165269 type Work @default.
• W4311165269 citedByCount "1" @default.
• W4311165269 countsByYear W43111652692023 @default.
• W4311165269 crossrefType "journal-article" @default.
• W4311165269 hasAuthorship W4311165269A5000652124 @default.
• W4311165269 hasAuthorship W4311165269A5003565644 @default.
• W4311165269 hasAuthorship W4311165269A5009598734 @default.
• W4311165269 hasAuthorship W4311165269A5012379209 @default.
• W4311165269 hasAuthorship W4311165269A5012867126 @default.
• W4311165269 hasAuthorship W4311165269A5013463645 @default.
• W4311165269 hasAuthorship W4311165269A5021462287 @default.
• W4311165269 hasAuthorship W4311165269A5040980936 @default.
• W4311165269 hasAuthorship W4311165269A5042410729 @default.
• W4311165269 hasAuthorship W4311165269A5043092566 @default.
• W4311165269 hasAuthorship W4311165269A5045583717 @default.
• W4311165269 hasAuthorship W4311165269A5047010658 @default.
• W4311165269 hasAuthorship W4311165269A5048240683 @default.
• W4311165269 hasAuthorship W4311165269A5051368970 @default.
• W4311165269 hasAuthorship W4311165269A5055669649 @default.
• W4311165269 hasAuthorship W4311165269A5063961568 @default.
• W4311165269 hasAuthorship W4311165269A5070047090 @default.
• W4311165269 hasAuthorship W4311165269A5086415657 @default.
• W4311165269 hasConcept C134306372 @default.
• W4311165269 hasConcept C161790260 @default.
• W4311165269 hasConcept C178790620 @default.
• W4311165269 hasConcept C185592680 @default.
• W4311165269 hasConcept C197336794 @default.
• W4311165269 hasConcept C19831878 @default.
• W4311165269 hasConcept C21951064 @default.
• W4311165269 hasConcept C2776573223 @default.
• W4311165269 hasConcept C2780035454 @default.
• W4311165269 hasConcept C29730261 @default.
• W4311165269 hasConcept C33923547 @default.
• W4311165269 hasConcept C55493867 @default.
• W4311165269 hasConcept C71240020 @default.
• W4311165269 hasConcept C71924100 @default.
• W4311165269 hasConcept C98274493 @default.
• W4311165269 hasConceptScore W4311165269C134306372 @default.
• W4311165269 hasConceptScore W4311165269C161790260 @default.

• next