Matches in SemOpenAlex for { <https://semopenalex.org/work/W2061668085> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W2061668085 abstract "SGI‐110 is a second generation hypomethylating agent being developed for treatment in myelodysplastic syndrome (MDS) and solid tumor malignancies. In previous work, SGI‐110 has demonstrated potent in vivo activity in a number of tumor types, including non‐hematological cell lines. Current efforts are underway to optimize formulation and delivery of SGI‐110 for first‐in‐human (FIH) studies. In animals, SGI‐110 is well‐tolerated across multiple species utilizing multiple routes of drug delivery. Tolerability studies have been performed in mouse, rat, and rabbit models with multiple dose routes and schedules. Myelosuppression is an observed toxicity endpoint for hypomethylating agents. Hence, myelotoxic effects were investigated by comparing RBCs and bone marrow cellularity of mice treated with and without SGI‐110. Mice dosed with SGI‐110 for five consecutive days showed a significant decrease in RBCs at the end of the dosing period and a continued decrease one week after dosing. Bone marrow cellularity also showed a decrease at the end of dosing, but recovered to near normal levels one week later. Interestingly, RBCs from SGI‐110 treated mice were elevated in the bone marrow after the dosing period. Pyrosequencing methylation analysis of colon samples was also evaluated in this study. A significant decrease in B1 methylation was observed in colon samples of treated mice, indicating global DNA methylation is being inhibited. Decreased levels in several hematology parameters and decreases in bone marrow cellularity were also observed in rat and rabbit studies after five consecutive days of SGI‐110 dosing. Increased dosing frequency, while maintaining the same total dose per week, appears to result in increased toxicity. Previous pharmacokinetic studies have shown that SGI‐110 rapidly metabolizes to decitabine, an FDA‐approved drug for MDS. Multiple formulations and different routes of delivery were examined to determine the optimal dose form to be used in FIH studies. Subcutaneous dosing results in bioavailability that is similar to that of intravenous dosing. Subcutaneous dosing appears to reduce the Cmax while maintaining similar AUC values when compared to intravenous dosing. Similar results in pharmacokinetic parameters are observed when the delivery vehicle is changed from an aqueous to non‐aqueous formulation. SGI‐110 is a novel hypomethylating agent that is well‐tolerated in rodent models, provides excellent PK exposure, and demonstrates inhibition of DNA methylation in a mouse model. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):A190." @default.
- W2061668085 created "2016-06-24" @default.
- W2061668085 creator A5019130673 @default.
- W2061668085 creator A5020548821 @default.
- W2061668085 creator A5021674646 @default.
- W2061668085 creator A5023931973 @default.
- W2061668085 creator A5037979147 @default.
- W2061668085 creator A5059551301 @default.
- W2061668085 creator A5064715411 @default.
- W2061668085 creator A5069372582 @default.
- W2061668085 creator A5071964860 @default.
- W2061668085 creator A5078859244 @default.
- W2061668085 creator A5081168039 @default.
- W2061668085 date "2009-12-10" @default.
- W2061668085 modified "2023-09-27" @default.
- W2061668085 title "Abstract A190:In vivoactivity of SGI‐110, a novel hypomethylating agent for treatment in hematology and solid malignancies" @default.
- W2061668085 doi "https://doi.org/10.1158/1535-7163.targ-09-a190" @default.
- W2061668085 hasPublicationYear "2009" @default.
- W2061668085 type Work @default.
- W2061668085 sameAs 2061668085 @default.
- W2061668085 citedByCount "0" @default.
- W2061668085 crossrefType "proceedings-article" @default.
- W2061668085 hasAuthorship W2061668085A5019130673 @default.
- W2061668085 hasAuthorship W2061668085A5020548821 @default.
- W2061668085 hasAuthorship W2061668085A5021674646 @default.
- W2061668085 hasAuthorship W2061668085A5023931973 @default.
- W2061668085 hasAuthorship W2061668085A5037979147 @default.
- W2061668085 hasAuthorship W2061668085A5059551301 @default.
- W2061668085 hasAuthorship W2061668085A5064715411 @default.
- W2061668085 hasAuthorship W2061668085A5069372582 @default.
- W2061668085 hasAuthorship W2061668085A5071964860 @default.
- W2061668085 hasAuthorship W2061668085A5078859244 @default.
- W2061668085 hasAuthorship W2061668085A5081168039 @default.
- W2061668085 hasConcept C104317684 @default.
- W2061668085 hasConcept C111113717 @default.
- W2061668085 hasConcept C112705442 @default.
- W2061668085 hasConcept C126322002 @default.
- W2061668085 hasConcept C150194340 @default.
- W2061668085 hasConcept C150903083 @default.
- W2061668085 hasConcept C190727270 @default.
- W2061668085 hasConcept C194409129 @default.
- W2061668085 hasConcept C197934379 @default.
- W2061668085 hasConcept C207001950 @default.
- W2061668085 hasConcept C2776012956 @default.
- W2061668085 hasConcept C2777288759 @default.
- W2061668085 hasConcept C2778375690 @default.
- W2061668085 hasConcept C2780007613 @default.
- W2061668085 hasConcept C55493867 @default.
- W2061668085 hasConcept C71924100 @default.
- W2061668085 hasConcept C86803240 @default.
- W2061668085 hasConcept C98274493 @default.
- W2061668085 hasConceptScore W2061668085C104317684 @default.
- W2061668085 hasConceptScore W2061668085C111113717 @default.
- W2061668085 hasConceptScore W2061668085C112705442 @default.
- W2061668085 hasConceptScore W2061668085C126322002 @default.
- W2061668085 hasConceptScore W2061668085C150194340 @default.
- W2061668085 hasConceptScore W2061668085C150903083 @default.
- W2061668085 hasConceptScore W2061668085C190727270 @default.
- W2061668085 hasConceptScore W2061668085C194409129 @default.
- W2061668085 hasConceptScore W2061668085C197934379 @default.
- W2061668085 hasConceptScore W2061668085C207001950 @default.
- W2061668085 hasConceptScore W2061668085C2776012956 @default.
- W2061668085 hasConceptScore W2061668085C2777288759 @default.
- W2061668085 hasConceptScore W2061668085C2778375690 @default.
- W2061668085 hasConceptScore W2061668085C2780007613 @default.
- W2061668085 hasConceptScore W2061668085C55493867 @default.
- W2061668085 hasConceptScore W2061668085C71924100 @default.
- W2061668085 hasConceptScore W2061668085C86803240 @default.
- W2061668085 hasConceptScore W2061668085C98274493 @default.
- W2061668085 hasLocation W20616680851 @default.
- W2061668085 hasOpenAccess W2061668085 @default.
- W2061668085 hasPrimaryLocation W20616680851 @default.
- W2061668085 hasRelatedWork W1018556295 @default.
- W2061668085 hasRelatedWork W1627163318 @default.
- W2061668085 hasRelatedWork W2018615358 @default.
- W2061668085 hasRelatedWork W2020863305 @default.
- W2061668085 hasRelatedWork W2037577456 @default.
- W2061668085 hasRelatedWork W2070716213 @default.
- W2061668085 hasRelatedWork W2082839259 @default.
- W2061668085 hasRelatedWork W2090162658 @default.
- W2061668085 hasRelatedWork W2097868846 @default.
- W2061668085 hasRelatedWork W2118908256 @default.
- W2061668085 hasRelatedWork W2145364998 @default.
- W2061668085 hasRelatedWork W2166379274 @default.
- W2061668085 hasRelatedWork W2253778139 @default.
- W2061668085 hasRelatedWork W2256817194 @default.
- W2061668085 hasRelatedWork W2264924307 @default.
- W2061668085 hasRelatedWork W2323720734 @default.
- W2061668085 hasRelatedWork W2496259455 @default.
- W2061668085 hasRelatedWork W2516859183 @default.
- W2061668085 hasRelatedWork W2743022376 @default.
- W2061668085 hasRelatedWork W2979589406 @default.
- W2061668085 isParatext "false" @default.
- W2061668085 isRetracted "false" @default.
- W2061668085 magId "2061668085" @default.
- W2061668085 workType "article" @default.