Ascent Scientific Ltd Launch Novel Dynamin Inhibitor Dyngo-4a(TM) with Children's Medical Research Institute and University of Newcastle
Published: Oct 31, 2011
Ascent Scientific have recently launched a range of dynamin inhibitors which have application for researchers investigating cell signalling pathways, the cell cycle, cellular division and a range of medical conditions including cancer, infectious diseases and neurological disorders. These compounds can be purchased independently or as part of kits which include chemically distinct dynamin inhibitors and their structurally similar inactive control compounds. Ascent Scientific is continuing to expand this exciting new area by adding Dyngo-4a™ to the dynamin inhibitor range.
Dynamin is a key protein involved in the cellular process of endocytosis. Endocytic pathways are utilised by viruses and toxins to gain entry into cells - the botulinum neurotoxins (BoNTs) are examples of such toxins and are responsible for the paralytic illness botulism.
The novel and potent dynasore analogue, Dyngo-4a™, inhibits dynamin to abolish endocytotic internalisation of these BoNTs. This inhibits BoNT-induced paralysis and delays onset of botulism. Dyngo-4a™ and these studies of BoNT were recently published in the Journal of Biological Chemistry by a collaboration involving scientists from the University of Queensland, Children’s Medical Research Institute and University of Newcastle, in a paper entitled “Dynamin inhibition blocks botulinum neurotoxin type-a endocytosis in neurons and delays botulism” (Harper CB et al., 2011, JBC Aug 5 Epub ahead of print).
One of the collaborators on the botulism study and a co-inventor of the Dyngo-4aTM compound, Professor Phil Robinson from Children’s Medical Research Institute said “The development of Dyngo-4aTM as a much more potent analogue of dynasore will enable researchers to overcome some of the non-specific binding problems observed with the use of dynasore. Dyngo-4aTM is greatly improved in potency and has greatly reduced non-specific binding properties, making it of much broader utility to cell biologists. The new compound has a distinct mechanism of action to Dynole-34-2TM yet has about the same in-cell potency. The use of multiple dynamin inhibitors from different chemical classes and with distinct molecular mechanisms of action can improve the supportive evidence for dynamin’s role in a particular cellular process or pathway”.
Steve Roome PhD, General Manager for Ascent Scientific, commented “The addition of Dyngo-4a™ to the exciting dynamin inhibitor range provides researchers with novel ways to inhibit dynamin activity and modulate endocytosis. The recent paper by Harper et al. shows that dynamin inhibitors like Dyngo-4a™ can have marked physiological effects.”
Dynamin inhibitors and their inactive controls that are currently available from Ascent Scientific include:
Novel, highly potent dynamin inhibitor (IC50 values are 380 nM and 2.6 µM for dynamin I and II respectively). An analogue of dynasore (Asc-192) that is up to 40 times more potent in vitro and up to 10 times more potent in inhibiting clathrin-mediated endocytosis. Prevents botulinum neurotoxin A uptake and internalisation thereby preventing SNAP25 cleavage. Inhibits BoNT-induced paralysis and delays onset of botulism.
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).
Negative control for Iminodyn-22TM (Asc-461), for use in cell based assays. Potently inhibits dynamin I and II GTPase activity in vitro (IC50 values are 330 nM and 440 nM respectively), but does not affect dynamin-mediated endocytosis in cells (IC50 values are =300 µM for receptor-mediated and synaptic vesicle endocytosis).
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.
Negative control molecule for use with Dynole 34-2TM (Asc-463). Displays no significant activity at dynamin I or II (up to 300 µM).
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).
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.
Cell permeable dynamin I and dynamin II inhibitor (IC50 = 1.9 and 4.4 µM for inhibition of dynamin I and II GTPase respectively). Targets the pleckstrin homology (PH) (lipid binding) domain. Competitive with phospholipid and noncompetitive with GTP. Inhibits receptor-mediated endocytosis (IC50 = 6.7 µM). Inhibits cancer cell growth.
Pro-Myristic Acid (Asc-476)
Negative control molecule for use with MiTMABTM (Asc-466) and OcTMABTM (Asc-467). Pro-Myristic acid is an in vitro inhibitor of dynamin I and II, targeting the PH (lipid binding) domain. Although cell permeable, it is rapidly broken down by cellular esterases to release intracellular myristic acid, which is not a dynamin inhibitor. It can therefore be used as a negative control in cell-based studies with MiTMABTM and/or OcTMABTM.
Sold under exclusive license from Children’s Medical Research Institute and Newcastle Innovation Ltd. IminodynTM, Iminodyn-22TM, Iminodyn-17 TM, DynoleTM, Dynole-34-2TM, Dynole-31TM, RTIL-13TM, MiTMABTM, OcTMABTM, DyngoTM and Dyngo-4aTM are trademarks of Children’s Medical Research Institute and Newcastle Innovation Ltd.
About the Children's Medical Research Institute
Established in 1958 by Sir Lorimer Dods' goals to advance and enhance health care for the benefit of the community. Today, CMRI is committed to excellence in biomedical science, engaging in fundamental research into the causes, prevention, early diagnosis and relief or cure of disease in children. CMRI scientists aim to understand the basic inner workings of our cells and to find better ways to prevent and treat diseases which rob children of their chance at a long and healthy life. Many diseases that affect children, such as cancer and epilepsy, have the same origins in adults. www.cmri.org.au
About The University of Newcastle
Established in 1965, the University of Newcastle in regional NSW (according to the Lonely Planet's guide, the 9th must visit city on the planet) is the most research intensive university outside of an Australian capital city. Ranked ninth among Australia's universities for research, Newcastle's reputation is for innovation, excellence and research with impact. www.newcastle.edu.au
About Bio-Link Australia
Bio-Link Australia Pty Ltd. is a life sciences commercialisation company which facilitates partnerships in the biopharma and diagnostic industries. Bio-Link has offices in Sydney and Melbourne, Australia, and clients including leading Australian and international medical research institutions and biotechnology companies. www.bio-link.com.
About Ascent Scientific, an Abcam company
Ascent Scientific’s mission is to progress research by providing biochemicals of high purity and exceptional quality to researchers around the world. Ascent Scientific products have been cited in numerous peer-reviewed publications. The high purity range includes agonists, antagonists, ion channel modulators, enzyme inhibitors and signalling tools for research in areas such as glutamate, GABA, ion channels, cannabinoids, opioids, 5-HT and more. www.ascentscientific.com
Professor Phil Robinson
Children's Medical Research Institute
+612 8865 2800
Dr Christian Toouli
+612 9571 8815
Professor Adam McCluskey
University of Newcastle
Phone: +612 4921 6486
Dr Steve Roome
+44 (0)117 982 9988