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Dataset results
19 results for “ACVR1”
Activin A receptor, type I (ACVR1); A Target Enabling Package
<p>Germline gain of function mutations in the gene <em>ACVR1</em> encoding the BMP receptor ALK2 lead to the rare congenital syndrome FOP in which aberrant signalling through the BMP signalling pathway leads to progressive heterotopic ossification in muscle and connective tissue. Identical somatic mutations have been identified in 25% of cases of the childhood brain tumour DIPG. Both conditions affect young children and have no approved therapies. Highly selective ALK2 kinase inhibitors are therefore desirable to achieve chronic treatment of children with safety. We prepared recombinant ALK2 kinase domain and solved structures of ALK2 in complex with new ATP-competitive inhibitors. We identified a novel allosteric pocket in the ALK2 kinase domain and took advantage of these structures to perform crystallographic fragment screening (XChem) using both a standard poised fragment library and a new mini-fragment library. This work identified a poised fragment for development as an allosteric ALK2 inhibitor, as well as mini-fragments exploiting new areas of the ATP and substrate binding pockets. <em>In vitro</em> and cellular assays are available to advance these compounds for drug development in collaboration with patient groups.</p>
Deposition of ALK2 (ACVR1) co-crystallised with M4K2117 (PDB: 6SRH)
<p>Desposition of the structure of ALK2 co-crystallised with the compound M4K2117 in the PDB database with code 6SRH.</p> <p>You can read more about it over on the <a href="https://openlabnotebooks.org/?p=3575&preview=true">Open Lab Notebooks project.</a></p> <p> </p>
Deposition of crystal structure of ACVR1 / ALK2 with M4K2009
<p>Deposition of the structure of ACVR1 / ALK2 bound to the compound M4K2009</p> <p>You can read more over at <a href="https://openlabnotebooks.org/?p=3643&preview=true">Open Lab Notebooks</a></p>
Purification of ACVR1 for co-crystallisation with LDN-193189 and other compounds
<p>Purification of constitutively active ACVR1 for co-crystallisation with LDN-193189 and three other compounds.</p>
Efficacy of inhibitor on wild-type ACVR1 and R206H mutant in C2C12 cells (by DLA)
<p>There are concerns that compounds that are effective in inhibiting ALK2 by occupying its ATP-binding pocket might have reduced efficacy against mutant ALK2. That will be undesirable since the compounds should also target the mutant gain-of-function ALK2 in DIPG cells. The following experiment takes advantage of the fact that ALK2-R206H mutant confers a neofunction of being activated by Activin A (not activating towards wild-type ALK2). Therefore, using Activin A as the stimulation ligand, the effectiveness of inhibition on ALK2-R206H can be specifically determined. BMP6 which activates both wild-type ALK2 and ALK2-R206H is also included.</p>
Determining the suitability of C2C12 and HEK293 in dual luciferase assay (DLA) for ACVR1 (ALK2) and TGFBR1 (ALK5)
<p>Aside from having high potency towards ACVR1/ALK2, inhibitor compounds ideally should be highly selective and not target other members of the Transforming Growth Factor beta (TGFb) superfamily. TGFBR1/ALK5 is selected for off-target screening because of its potential role in cardiac functions.</p>
ACVR1 1.25 Å and 2 Å datasets for M4K2117 and M4K2121
<p>Autoprocessed .mtz files for ACVR1 bound to M4K2117 and M4K2121</p>
An Observational Pre-post Study to Observe if the Off Label Use of Anti-IL1 Therapies, Such as Anakinra or Canakinumab, Can Block ACVR1-induced Flare Activity and Heterotopic Ossification in FOP
ClinicalTrials.gov study NCT06724562. IPD Sharing: YES. Countries: 1. Publications: 2.
Data from: Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop
<p><span><span><span><span><span><span><span><span><span><span><span>Activin A functions in BMP signaling in two ways: it either engages ACVR1B to activate Smad2/3 signaling or binds ACVR1 to form a non-signaling complex (NSC). Although the former property has been studied extensively, the roles of the NSC remain unexplored. The genetic disorder fibrodysplasia ossificans progressiva (FOP) provides a unique window into ACVR1/Activin A signaling because in that disease Activin can either signal through FOP-mutant ACVR1 or form NSCs with wild type ACVR1. To explore the role of the NSC, we generated 'agonist-only' Activin A muteins that activate ACVR1B but cannot form the NSC with ACVR1. Using one of these muteins we demonstrate that failure to form the NSC in FOP results in more severe disease pathology. These results provide the first evidence for a biological role for the NSC <i>in vivo</i> and pave the way for further exploration of the NSC's physiological role in corresponding knock-in mice.</span></span></span></span></span></span></span></span></span></span></span></p>
Data from: Activin A forms a non-signaling complex with ACVR1 and type II Activin/BMP receptors via its finger 2 tip loop
Open the record for dataset details and reuse information.
RNA data of human FOP patients-derived iPSCs treated with ACVR1 R206H mutant-targeting AAVs
GEO Series GSE213579. Homo sapiens. 6 samples. Type: Expression profiling by high throughput sequencing.
RNA Sequencing Data in control and Acvr1:Nfatc1Cre mouse aortic valve tissues (4 months old)
GEO Series GSE122106. Mus musculus. 6 samples. Type: Expression profiling by high throughput sequencing.
RNAseq of nestin-expressing murine brainstem progenitors infected with ACVR1 WT or R206H ACVR1 with and without H3.1K27M
GEO Series GSE125627. Mus musculus. 12 samples. Type: Expression profiling by high throughput sequencing.
Mutant ACVR1 Arrests Glial Cell Differentiation to Drive Tumorigenesis in Pediatric Gliomas
GEO Series GSE142776. Mus musculus. 10 samples. Type: Expression profiling by high throughput sequencing.
Differential gene expression in mACVR1 NS v wt-ACVR1 NS.
GEO Series GSE148732. Mus musculus. 6 samples. Type: Expression profiling by high throughput sequencing.
Recapitulation of the pro-inflammatory signature of monocytes with ACVR1 mutation using FOP patient-derived iPSCs
GEO Series GSE183525. Homo sapiens. 42 samples. Type: Expression profiling by array.
ACVR1-mutant posterior fossa ependymoma
GEO Series GSE196013. Homo sapiens. 7 samples. Type: Methylation profiling by genome tiling array.
ACVR1-mediated glycolytic reprogramming promotes histone lactylation and neuronal pyroptosis in neuropathic pain [RNA-Seq]
GEO Series GSE306455. Mus musculus. 9 samples. Type: Expression profiling by high throughput sequencing.
ACVR1-mediated glycolytic reprogramming promotes histone lactylation and neuronal pyroptosis in neuropathic pain {ChIP-seq]
GEO Series GSE306458. Mus musculus. 12 samples. Type: Genome binding/occupancy profiling by high throughput sequencing.
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
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DANDI Archive for NWB datasets
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International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.