Deletion of Itpkb or treatment with Itpkb inhibitors blocks T-cell dependent antibody responses in vivo and prevents T cell driven arthritis in rats. These data identify Itpkb as an essential

GNF362 is a selective, potent, and orally bioavailable inhibitor of inositol trisphosphate 3’ kinase B (Itpkb) with an IC50 of 9 nM. GNF362 also inhibits Itpka and Itpkc with IC50 values of 20 nM and 19 nM, respectively.

Future studies with sub-optimal Akt/mTOR inhibitor concentrations not affecting WT thymocytes but still reversing the Itpkb-/-phenotype, with complex genetic models and with inhibitors of β-selection effectors unaffected by Itpkb will be needed to more conclusively distinguish between specific causative roles for the Akt/mTORC1 and metabolic hyperactivity and mere remaining sensitivity of 2005-04-26 · cytoplasm, cytosol, nucleus, inositol hexakisphosphate kinase activity, inositol-1,4,5-trisphosphate 3-kinase activity, kinase activity, cellular response to calcium ion, inositol phosphate biosynthetic process, inositol phosphate metabolic process, inositol trisphosphate metabolic process In turn, inositol 1,4,5-trisphosphate 3-kinase B (Itpkb) phosphorylates IP 3 to negatively regulate and thereby tightly control Ca 2 1 fluxes that are essential for mature T-cell activation and differentiation and protection from cell death. Itpkb pathway inhibition increases intracellular Ca 21 Does Itpkb Inhibition have Therapeutic Potential in Human Diseases? The T and B cell defects in germline Itpkb −/− mice sparked efforts to develop specific and selective Itpkb small-molecule inhibitors as potential therapeutics for autoimmune disorders or transplant rejection, reviewed in detail in Ref. (8, 149). Moreover, Akt inhibition reduced RMA/S-induced ItpkB −/− NK cell hyperdegranulation to inhibitor-untreated WT NK cell levels (22.3% vs 20.7%; Figure 7A-B). The similar abilities of cell-permeable IP 4 , PI3K, or Akt inhibitors to reverse the hyperdegranulation of ItpkB −/− NK cells are consistent with a model in which IP 4 limits NK cell degranulation by antagonizing NKR-induced Akt recruitment by PI3K/PIP 3 . Inhibition of the Inositol Kinase Itpkb Augments Calcium Signaling in Lymphocytes and Reveals a Novel Strategy to Treat Autoimmune Disease PLOS ONE , Dec 2019 Andrew T. Miller , Carol Dahlberg , Mark L. Sandberg , Ben G. Wen , Daniel R. Beisner , John A. H. Hoerter , Albert Parker , Christian Schmedt , Monique Stinson , Jacqueline Avis , et al. Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease.

Itpkb inhibitor

The Parkinson's disease-associated gene ITPKB protects against α-synuclein aggregation by regulating ER-to-mitochondria calcium release. In mouse Neuro-2a neuroblastoma cells, Itpkb overexpression was associated with increased cell apoptosis and increased β-secretase 1 activity leading to overproduction of amyloid-β peptides. In this cellular model, an inhibitor of mitogen-activated kinase kinases 1/2 completely prevented overproduction of amyloid-β peptides. Itpkb pathway inhibition increases intracellular Ca2+, induces apoptosis of activated T-cells, and can control T-cell mediated autoimmunity. Here, we employed genetic and pharmacological approaches to inhibit Itpkb signaling as a means of controlling graft-versus-host disease (GVHD). Inhibition of inositol kinase B controls acute and chronic graft-versus-host disease.

Compounds and compositions as itpkb inhibitors. C07D491/048 - C07D413/14 - containing three or more hetero rings.

PDS5B. PDS5, regulator of BMP and activin membrane-bound inhibitor homolog itpka, itpkb, itpkc, insp3 3-kinase, ip3k, ip3k-a, ip3kb, insp3kinase, ins(1,4,5)p3 kinase, inositol 1,4,5-trisphosphate 3-kinase c, more. top print hide 112 entries Aug 1, 2016 These data indicate an inhibitory effect of.

Dec 3, 2019 GNF362 is a selective, potent, and orally bioavailable inhibitor of Itpkb and also inhibits Itpka and Itpkc, and It blocks T cell-driven autoimmune

MedChemExpress provides thousands of inhibitors, modulators and agonists with high purity and quality, excellent customer reviews, precise and professional product citations, tech support and prompt delivery. 2020-01-02 · We next explored a relevant translational Itpkb inhibition approach using a novel, orally potent (IC 50 = 9 nM), selective Itpkb inhibitor, GNF362. 5 Irradiated B10.BR recipients of B6 BM+WT T cells were administered vehicle or GNF362 (days 0-42). ITPKB inhibition or knockdown increases intracellular calcium levels in neurons, leading to an accumulation of calcium in mitochondria that increases respiration and inhibits the initiation of autophagy, suggesting that ITPKB regulates α-synuclein pathology by inhibiting ER-to-mitochondria calcium transport. Furthermore, the effects of 2015-06-29 · Itpkb inhibitors block T cell-driven autoimmune disease. Rat antigen-induced arthritis (rAIA) is a well-studied animal model of arthritis, due to its similarities with human Rheumatoid Arthritis (RA), and the involvement of T lymphocytes .

319449792 - EP 2167498 A1 20100331 - COMPOUNDS AND COMPOSITIONS AS ITPKB INHIBITORS - [origin: WO2008157210A1] The invention provides a novel class of compounds of formula (I), pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or dysregulated B cell activities, particularly diseases or Emerging approaches to treat immune disorders target positive regulatory kinases downstream of antigen receptors with small molecule inhibitors. Here we Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.
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MedChemExpress provides thousands of inhibitors, modulators and agonists with high purity and quality, excellent customer reviews, precise and professional product citations, tech support and prompt delivery. ITPKB inhibition or knockdown increases intracellular calcium levels in neurons, leading to an accumulation of calcium in mitochondria that increases respiration and inhibits the initiation of autophagy, suggesting that ITPKB regulates α-synuclein pathology by inhibiting ER-to-mitochondria calcium transport. Furthermore, the effects of small-molecule inhibitors BAMB-4 and GNF362 are reported to specifically inhibit ITPK isoforms (23–25).

nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha ITPKB, inositol-trisphosphate 3-kise B [Source:HGNC Symbol;Acc:6179] Secretory leukocyte peptidase inhibitor OS=Pongo abelii GN=SLPI PE=4 SV=1 Uncharacterized protein OS=Pongo abelii GN=ITPKB PE=4 SV=1 Peptidase inhibitor R3HDML OS=Mus musculus GN=R3hdml PE=3 SV=1 Inositol 1,4,5-trisphosphate 3-kinase B OS=Mus musculus GN=Itpkb PE=2 SV=1 GNF362 is a selective, potent, and orally bioavailable inhibitor of inositol trisphosphate 3’ kinase B (Itpkb) with an IC50 of 9 nM. GNF362 also inhibits Itpka and Itpkc with IC50 values of 20 nM and 19 nM, respectively.
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The invention provides a novel class of compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with abnormal or dysregulated B cell activities, particularly diseases or disorders that involve aberrant activation of inositol 1,4,5-trisphosphate 3-kinase B (ITPKb).

These ion channels are required for salt and fluid secretion from epithelial cells, for cell volume homeostasis, and for electrical excitability in neurons and smooth muscle. The enzyme ITPK1 (inositol 1,3,4-triphosphate 5/6 kinase) is the