https://nova.newcastle.edu.au/vital/access/manager/Index ${session.getAttribute("locale")} 5 https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:39597 Wed 15 Jun 2022 12:54:03 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:38143 Wed 15 Feb 2023 11:16:01 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:47111 Wed 14 Dec 2022 10:19:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10991 Wed 11 Apr 2018 14:47:28 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:18276 Wed 11 Apr 2018 12:33:19 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20085 Wed 11 Apr 2018 12:17:41 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27739 Wed 11 Apr 2018 11:56:44 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34617 Wed 09 Feb 2022 15:55:15 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:34053 Wed 04 Sep 2019 09:39:49 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:21743 50 values ≤10 μM, making the Rhodadyn series among the most active dynamin inhibitors reported. Two analogues were highly effective at blocking receptor-mediated endocytosis: C10 and D10 with IC_50(RME) = 7.0 ± 2.2 and 5.9 ± 1.0 μM, respectively. These compounds are equipotent with the best reported in-cell dynamin inhibitors.]]> Wed 02 Dec 2015 10:02:08 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20160 36-fold reduced activity against rings, suggesting that they can discriminate between helical or ring oligomerization states. 4a and 6a inhibited dynamin-dependent endocytosis of transferrin in multiple cell types (IC50 of 5.7 and 5.8 μM, respectively), at least sixfold more potently than dynasore, but had no effect on dynamin-independent endocytosis of cholera toxin. 4a also reduced synaptic vesicle endocytosis and activity-dependent bulk endocytosis in cultured neurons and synaptosomes. Overall, 4a and 6a are improved and versatile helical dynamin and endocytosis inhibitors in terms of potency, non-specific binding and cytotoxicity. The data further suggest that the ring oligomerization state of dynamin is not required for clathrin-mediated endocytosis.]]> Tue 24 Aug 2021 14:23:34 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50247 Tue 11 Jul 2023 14:16:11 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:41385 Tue 02 Aug 2022 15:55:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:54007 Thu 25 Jan 2024 13:53:31 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:26886 Thu 16 Mar 2017 16:43:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:31291 Thu 13 Jan 2022 10:28:35 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:44082 in vitro and orthotopic tumour growth in vivo. Dynamin inhibition reduced glioblastoma cell line viability and suppressed neurosphere formation and migration of GSCs. Tumour growth was reduced by CyDyn 4-36 treatment. Dynamin 2 inhibition therefore represents a novel approach for stem cell-directed Glioblastoma therapy.]]> Thu 06 Oct 2022 15:06:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:32119 (CME) = 65.9 ± 7.7 to 3.7 ± 1.1 mM), which makes this series among the more potent inhibitors of dynamin and CME yet reported. In CME and growth inhibition cell-based assays, the data obtained was consistent with dynamin inhibition. CEREP ExpresS profiling identified off-target effects at the cholecystokinin, dopamine D₂, histamine H₁ and H₂, melanocortin, melatonin, muscarinic M₁ and M₃, neurokinin, opioid KOP and serotonin receptors.]]> Thu 03 May 2018 12:18:53 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20908 Thu 01 Aug 2019 17:22:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7404 Sat 24 Mar 2018 08:42:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8246 Sat 24 Mar 2018 08:40:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8338 Sat 24 Mar 2018 08:37:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1956 Sat 24 Mar 2018 08:33:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1723 Sat 24 Mar 2018 08:27:23 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2267 Sat 24 Mar 2018 08:26:55 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11175 Sat 24 Mar 2018 08:14:32 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9963 Sat 24 Mar 2018 08:14:26 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11334 Sat 24 Mar 2018 08:13:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11336 Sat 24 Mar 2018 08:13:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10254 Sat 24 Mar 2018 08:13:07 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:21428 50 ≈ 18 μM). A second library targeting the 4-aminobenzyl moiety was developed, and four analogues displayed comparable activity (26, 27, 28, 34 with IC₅₀ values of 22, 16, 15, and 15 μM respectively) with a further four (24, 25, 32, 33) more active than 18 with IC₅₀ values of 10, 6.9, 12, and 10 μM, respectively. Docking studies rationalized the structure–activity relationship (SAR) with the biological data. 3-Sulfo-N-benzyl-1,8-naphthalimide, potassium salt (25) with an IC50 ≈ 6.9 μM, is the most potent clathrin terminal domain–amphiphysin inhibitor reported to date.]]> Sat 24 Mar 2018 08:05:47 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:17425 Sat 24 Mar 2018 08:01:39 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:17423 TM, was sufficient to abolish BoNT/A-Hc internalization and BoNT/A-induced SNAP25 cleavage in hippocampal neurons. Dyngo-4a also interfered with BoNT/A-Hc internalization into motor nerve terminals. Furthermore, Dyngo-4a afforded protection against BoNT/A-induced paralysis at the rat hemidiaphragm. A significant delay of >30% in the onset of botulism was observed in mice injected with Dyngo-4a. Dynamin inhibition therefore provides a therapeutic avenue for the treatment of botulism and other diseases caused by pathogens sharing dynamin-dependent uptake mechanisms.]]> Sat 24 Mar 2018 08:01:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20084 Sat 24 Mar 2018 08:00:05 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:19893 Sat 24 Mar 2018 07:57:02 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20625 Sat 24 Mar 2018 07:55:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20674 Sat 24 Mar 2018 07:55:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:21262 Sat 24 Mar 2018 07:54:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:20159 Sat 24 Mar 2018 07:51:36 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5056 Sat 24 Mar 2018 07:48:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5000 Sat 24 Mar 2018 07:44:09 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27080 Sat 24 Mar 2018 07:40:44 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:28474 in silico docking studies. Docking studies predicted enhanced Pitstop® 2 family binding, not a loss of binding, within the Pistop® groove of the reported clathrin mutant invalidating recent assumptions of poor selectivity for this family of clathrin inhibitors.]]> Sat 24 Mar 2018 07:39:34 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27976 50 = 6.7 nM) led to a significant reduction in dynamin phosphorylation (10.3% vs. 27.3%; P < 0.001), acrosomal exocytosis (9.7% vs. 25.7%; P < 0.01), and in vitro fertilization (53% vs. 100%; P < 0.01). GSK3 was shown to be present in developing germ cells where it colocalized with dynamin in the peri-acrosomal domain. However, additional GSK3 was acquired by maturing mouse spermatozoa within the male reproductive tract, via a novel mechanism involving direct interaction of sperm heads with extracellular structures known as epididymal dense bodies. These data reveal a novel mode for the cellular acquisition of a protein kinase and identify a key role for GSK3 in the regulation of sperm maturation and acrosomal exocytosis.—Reid, A. T., Anderson, A. L., Roman, S. D., McLaughlin, E. A., McCluskey, A., Robinson, P. J., Aitken, R. J., Nixon, B. Glycogen synthase kinase 3 regulates acrosomal exocytosis in mouse spermatozoa via dynamin phosphorylation.]]> Sat 24 Mar 2018 07:38:43 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27301 50 2.6±0.7µm). They also inhibited dynamin II (dynII) at similar concentrations. Typical and atypical APDs not based on the phenothiazine scaffold were 8- to 10-fold less potent (haloperidol and clozapine) or were inactive (droperidol, olanzapine and risperidone). Kinetic analysis showed that phenothiazine-derived APDs were lipid competitive, while haloperidol was uncompetitive with lipid. Accordingly, phenothiazine-derived APDs inhibited dynI GTPase activity stimulated by lipids but not by various SH3 domains. All dynamin-active APDs also inhibited transferrin (Tfn) CME in cells at related potencies. Structure-activity relationships (SAR) revealed dynamin inhibition to be conferred by a substituent group containing a terminal tertiary amino group at the N2 position. Chlorpromazine was previously proposed to target AP-2 recruitment in the formation of clathrin-coated vesicles (CCV). However, neither chlorpromazine nor thioridazine affected AP-2 interaction with amphiphysin or clathrin. Super-resolution microscopy revealed that chlorpromazine blocks neither clathrin recruitment by AP-2, nor AP-2 recruitment, showing that CME inhibition occurs downstream of CCV formation. Overall, potent dynamin inhibition is a shared characteristic of phenothiazine-derived APDs, but not other typical or atypical APDs, and the data indicate that dynamin is their likely in-cell target in endocytosis.]]> Sat 24 Mar 2018 07:38:33 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:27742 Sat 24 Mar 2018 07:27:46 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:26323 NAr coupling with 1-fluoro-4-nitrobenzene. Microwave coupling of 4-morphilinoaniline 8 and 4-(piperazine-1-yl)aniline 9 with 2-(2,5-dichloropyrimidine-4-ylamino)-N-methylbenzamide 10, proved to be the most efficacious route to the target analogues 6 and 7. This hybrid methodology reduced the number of synthetic steps, gave enhanced overall yields and increased atom economy through step reduction and minimal requirement for chromatographic purification, relative to the original batch synthesis approach.]]> Sat 24 Mar 2018 07:24:11 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3266 Sat 24 Mar 2018 07:21:22 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:22263 in vitro induction of acrosomal exocytosis by progesterone, but not by the calcium ionophore A23187, and elicited a concomitant reduction of in vitro fertilization. In vivo treatment with these inhibitors also resulted in spermatozoa displaying reduced acrosome reaction potential. Dynamin 1 and 2 phosphorylation increased on progesterone treatment, and this was also selectively blocked by dynasore. On the basis of our collective data, we propose that dynamin could regulate specific membrane fusion events necessary for acrosomal exocytosis in mouse spermatozoa.]]> Sat 24 Mar 2018 07:17:38 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:23187 50 of 19.1 ± 0.3 and 18.5 ± 1.7 μM respectively). Compound 29 showed effective inhibition of clathrin-mediated endocytosis (IC_50(CME) 66 μM). The results introduce 29 as an optimised GTP-competitive lead Naphthaladyn™ compound for the further development of naphthalimide-based dynI GTPase inhibitors.]]> Sat 24 Mar 2018 07:10:29 AEDT ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:23772 Mon 23 Sep 2019 11:25:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:40592 Mon 08 Aug 2022 15:18:18 AEST ]]> https://nova.newcastle.edu.au/vital/access/manager/Repository/uon:50565 Fri 28 Jul 2023 11:27:49 AEST ]]>