Hydroxy-Dynasore

Hydroxy Dynasore (Dyngo-4a), a structural mimetic analog of Dynasore (HY-15304), is an improved, less cytotoxic and versatile dynamin inhibitor with IC₅₀ values ​​of 0.38 μM and 2.3 μM for brain recombinant dynamin I and recombinant mouse dynamin II, respectively. Hydroxy Dynasore inhibits dynamin-dependent transferrin endocytosis with an IC₅₀ of 5.7 μM. In Vitro:Dynamin is a large GTPase enzyme that severs membrane-bound clathrin-coated vesicles. Endocytosis internalizes portions of cells’ plasma membrane along with extracellular material, is fundamentally important in cell physiology.
Hydroxy Dynasore inhibits Dynamin I (Dyn I) activity with IC₅₀ values of 2.7 μM and 0.38 μM with or without 0.06% Tween-80 in the GTPase assay^[1].
Hydroxy Dynasore shows an IC₅₀ of 5.7 μM in clathrin-mediated endocytosis (CME) assay for inhibition of Tfn-A594 uptake in U2OS cells^[1].
Hydroxy Dynasore shows IC₅₀ values of 0.38 μM and 1.1 μM in absence of Tween-80, and exhibits IC₅₀ values of 4.9 μM and 30.0 μM in presence of Tween-80, respectively. Hydroxy Dynasore is 2.1-fold selective for DynI versus DynII from Sf21 cells and DynII (recombinant protein from Sf21 cells) in this GTPase assay^[1].
Hydroxy Dynasore prevents the uptake of BoNT/A-Hc in cultured hippocampal neurons and in motor nerve terminals^[2].
Hydroxy Dynasore (1-100μM; 20 min prior to the addition of Alexa Fluor 488-BoNT/A-Hc) results in depolarization of Hippocampal neurons, it dose-dependently inhibits internalization of Alexa Fluor 488-BoNT/A-Hc with an IC₅₀ of 16.0 ± 1.2 μM^[2].
In Vivo:Hydroxy Dynasore (intraperitoneal injection; 30 mg/kg; 1.5-2 h before BoNT/A injection) provides protection again BoNT/A-induced paralysis in the phrenic nerve-hemidiaphragm twitch model in CD-1 mice^[2].