Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022679750> ?p ?o ?g. }
Showing items 1 to 68 of
68
with 100 items per page.
- W2022679750 abstract "Formin-based cytoskeletal remodeling contributes to structural rearrangements that support an array of cellular demands, including chemotaxis and cell division. The Diaphanous formin family is managed in cells by Rho small GTP-binding proteins. Rho-GTP binding to the formin interferes with the intramolecular interaction between the Dia-inhibitory and -autoregulatory (DID & DAD) domains that flank the critical formin homology-2 (FH2) domain. The FH2 domain can then interact with microtubules to stabilize microtubule dynamics and loosely associate with barbed ends of polymeric actin filaments to add actin monomers. As a consequence of monomer consumption into filaments, formins also activate the MAL/MRTF-SRF transcription factor axis. DAD-derived peptides can activate formins in cells by interrupting the DID-DAD autoregulatory mechanism. We screened for drug-like small molecules with in vitro, cellular, and in vivo activities that could mimic the impact of DAD peptides. Two chemically similar molecules, called the Intramimics (IMMs) were identified. Both molecules (IMM-01 and -02) blocked DID-DAD binding in vitro, induced actin/microtubule stabilization in cells, activated SRF, and impaired cell-cycle progression. The IMMs each reduced xenograft tumor growth in mice. Due to their novel activity on formins, the IMMs represent an innovative therapeutic strategy for the study and treatment of diseases impacted by defects in cell structure, including autism, neurodegenerative disease, and cancer. Citation Format: Leanne L. Lash, Arthur S. Alberts. Small molecule activation of diaphanous-related formins as a novel anti-cancer strategy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2130. doi:10.1158/1538-7445.AM2013-2130" @default.
- W2022679750 created "2016-06-24" @default.
- W2022679750 creator A5023869395 @default.
- W2022679750 creator A5083273707 @default.
- W2022679750 date "2013-04-15" @default.
- W2022679750 modified "2023-09-25" @default.
- W2022679750 title "Abstract 2130: Small molecule activation of diaphanous-related formins as a novel anti-cancer strategy." @default.
- W2022679750 doi "https://doi.org/10.1158/1538-7445.am2013-2130" @default.
- W2022679750 hasPublicationYear "2013" @default.
- W2022679750 type Work @default.
- W2022679750 sameAs 2022679750 @default.
- W2022679750 citedByCount "0" @default.
- W2022679750 crossrefType "proceedings-article" @default.
- W2022679750 hasAuthorship W2022679750A5023869395 @default.
- W2022679750 hasAuthorship W2022679750A5083273707 @default.
- W2022679750 hasConcept C121608353 @default.
- W2022679750 hasConcept C125705527 @default.
- W2022679750 hasConcept C142669718 @default.
- W2022679750 hasConcept C1491633281 @default.
- W2022679750 hasConcept C185592680 @default.
- W2022679750 hasConcept C20418707 @default.
- W2022679750 hasConcept C2993400109 @default.
- W2022679750 hasConcept C53195969 @default.
- W2022679750 hasConcept C54355233 @default.
- W2022679750 hasConcept C55493867 @default.
- W2022679750 hasConcept C86803240 @default.
- W2022679750 hasConcept C95444343 @default.
- W2022679750 hasConcept C96232424 @default.
- W2022679750 hasConceptScore W2022679750C121608353 @default.
- W2022679750 hasConceptScore W2022679750C125705527 @default.
- W2022679750 hasConceptScore W2022679750C142669718 @default.
- W2022679750 hasConceptScore W2022679750C1491633281 @default.
- W2022679750 hasConceptScore W2022679750C185592680 @default.
- W2022679750 hasConceptScore W2022679750C20418707 @default.
- W2022679750 hasConceptScore W2022679750C2993400109 @default.
- W2022679750 hasConceptScore W2022679750C53195969 @default.
- W2022679750 hasConceptScore W2022679750C54355233 @default.
- W2022679750 hasConceptScore W2022679750C55493867 @default.
- W2022679750 hasConceptScore W2022679750C86803240 @default.
- W2022679750 hasConceptScore W2022679750C95444343 @default.
- W2022679750 hasConceptScore W2022679750C96232424 @default.
- W2022679750 hasLocation W20226797501 @default.
- W2022679750 hasOpenAccess W2022679750 @default.
- W2022679750 hasPrimaryLocation W20226797501 @default.
- W2022679750 hasRelatedWork W1556596990 @default.
- W2022679750 hasRelatedWork W1964873488 @default.
- W2022679750 hasRelatedWork W1979145729 @default.
- W2022679750 hasRelatedWork W2012349027 @default.
- W2022679750 hasRelatedWork W2017114015 @default.
- W2022679750 hasRelatedWork W2024095146 @default.
- W2022679750 hasRelatedWork W2030222262 @default.
- W2022679750 hasRelatedWork W2057477301 @default.
- W2022679750 hasRelatedWork W2064171532 @default.
- W2022679750 hasRelatedWork W2068131240 @default.
- W2022679750 hasRelatedWork W2074003465 @default.
- W2022679750 hasRelatedWork W2133898534 @default.
- W2022679750 hasRelatedWork W2164463504 @default.
- W2022679750 hasRelatedWork W2327568151 @default.
- W2022679750 hasRelatedWork W2529842825 @default.
- W2022679750 hasRelatedWork W2741901560 @default.
- W2022679750 hasRelatedWork W2943761896 @default.
- W2022679750 hasRelatedWork W3149090315 @default.
- W2022679750 hasRelatedWork W321811400 @default.
- W2022679750 hasRelatedWork W657172270 @default.
- W2022679750 isParatext "false" @default.
- W2022679750 isRetracted "false" @default.
- W2022679750 magId "2022679750" @default.
- W2022679750 workType "article" @default.