Ascent Scientific Licenses Novel Dynamin Toolkits
Ascent Scientific together with Children's Medical Research Institute and The University of Newcastle today announced that they have entered into a license, supply and distribution agreement for a range of small molecule dynamin inhibitors for research - these are novel tools for investigating cellular processes. The agreement was facilitated by Bio-Link Australia, a life sciences commercialisation company. Dynamin is a key protein involved in the cellular process of endocytosis, a process that involves the uptake and recycling of extracellular material by mammalian cells. Endocytic pathways are also utilised by viruses and toxins to gain entry into cells. Dynamin also participates in cell cycle progression and has shown to have critical roles in centrosome cohesion and cytokinesis. Dynamin inhibitors have applications for researchers investigating cell signalling pathways, the cell cycle and cellular division and a range of medical conditions including cancer, infectious diseases including HIV and botulism and neurological conditions such as epilepsy. The laboratories of Professor Adam McCluskey (University of Newcastle) and Professor Phillip Robinson (Children's Medical Research Institute) have developed the first set of rationally designed mechanism-based pharmacological inhibitors of dynamin. These inhibitors are a range of small molecule chemicals that stop endocytosis through inhibition of the GTPase dynamin, a key protein involved in the initiation and completion of endocytosis. McCluskey and Robinson have developed a unique portfolio of multiple classes of these small molecule dynamin inhibitors. These molecular classes selectively target different domains of dynamin providing novel research tools for understanding endocytosis biology and its role in intracellular processes and disease. Professor McCluskey said "We are very pleased that these dynamin inhibitors, which we designed and developed with the intent that they be utilized to further explore the chemical biology of dynamin and endocytosis biology, will now be available to researchers worldwide through Ascent Scientific." Professor Robinson remarked, "This palette of inhibitors provides a new means to regulate dynamin's activity by independent molecules and with more than one mechanism of action, allowing scientists to more definitively assign a particular biological function to dynamin. This strategy is more powerful than relying on the use of a sole inhibitor." Steve Roome PhD, Commercial Director for Ascent Scientific, comments "These groundbreaking tools provide a means for scientists to inhibit dynamin activity, and modulate endocytosis. Potent cell-permeable in vitro and in cell based inhibitors, together with control molecules are available individually, and in kit form - providing researchers with a variety of novel ways to explore dynamin-mediated cellular processes". The dynamin inhibitors (and their respective inactive control compounds) available from Ascent Scientific include: Iminodyn-22™ Potent, broad spectrum dynamin inhibitor. IC50 values are 450 nM and 390 nM for inhibition of dynamin I and II GTPase respectively). Binds to the GTPase domain at an allosteric site and displays uncompetitive antagonism with respect to GTP. Inhibits receptor mediated endocytosis (RME) and synaptic vesicle endocytosis (SVE) ( IC50 values are 10.7 and 108 μM respectively). Iminodyn-17™ Negative control for Iminodyn-22™, for use in cell based assays. Potently inhibits dynamin I and II GTPase activity in vitro (IC50 values are 330 nM and 440 nM), but does not affect dynamin-mediated endocytosis in cells (IC50 values are ≥300 μM for receptor-mediated and synaptic vesicle endocytosis). Dynole-34-2™ Potent, cell permeable dynamin I and dynamin II inhibitor (IC50 = 1.3 and 14.2 μM for inhibition of Dynamin I and II GTPase respectively). Targets the GTPase domain at an allosteric site. Potently inhibits receptor-mediated and synaptic vesicle endocytosis (IC50 values are 5 and 41.1 μM respectively). 15-fold more active than Dynasore (Asc-192) against dynamin I. Dynole-31™ Negative control molecule for use with Dynole 34-2™ (Asc-463). Displays no significant activity at dynamin I or II (up to 300 μM). RTIL-13™ Potent dynamin I and II inhibitor. Inhibits dynamin I GTPase (IC50 = 2.3 μM) and targets pleckstrin homology (PH) (lipid binding) domain. Inhibits receptor-mediated and synaptic vesicle endocytosis (IC50 values are 9.3 and 7.1 μM respectively). MiTMAB™ Cell permeable dynamin I and dynamin II inhibitor (IC50 = 3.1 and 8.4 μM for inhibition of dynamin I and dynamin II GTPase respectively). Targets the pleckstrin homology (PH) (lipid binding) domain. Competitive with phospholipid and noncompetitive with GTP. Inhibits receptor-mediated and synaptic vesicle endocytosis (IC50 values are 19.9 and 2.2 μM respectively). Inhibits cancer cell growth. OcTMAB™ Cell permeable dynamin