| Identification | Back Directory | [Name]
GSK2850163 | [CAS]
2121989-91-9 | [Synonyms]
GSK2850163
inhibit,IRE1,GSK 2850163,Inhibitor,Inositol requiring enzyme 1,GSK2850163,GSK-2850163
2,7-Diazaspiro[4.5]decane-7-carboxamide, 2-[(3,4-dichlorophenyl)methyl]-N-[(4-methylphenyl)methyl]-, (5R)- | [Molecular Formula]
C24H29Cl2N3O | [MDL Number]
MFCD30491882 | [MOL File]
2121989-91-9.mol | [Molecular Weight]
446.41 |
| Chemical Properties | Back Directory | [Boiling point ]
625.6±55.0 °C(Predicted) | [density ]
1.28±0.1 g/cm3(Predicted) | [storage temp. ]
2-8°C | [solubility ]
DMSO : 67.5 mg/mL (151.21 mM);Water : < 0.1 mg/mL (insoluble) | [form ]
oil | [pka]
13.81±0.20(Predicted) | [color ]
colorless to light yellow |
| Hazard Information | Back Directory | [Uses]
GSK2850163 is a novel inhibitor of inositol-requiring enzyme-1 alpha (IRE1α) which can inhibit IRE1α kinase activity and RNase activity with IC50s of 20 and 200 nM, respectively. | [Biochem/physiol Actions]
GSK2850163 is a highly selective inhibitor of inositol requiring enzyme-1 alpha (IRE1α) with dual activity: it inhibits IRE1α kinase activity with an IC50 value of 20 nM and RNase activity with an IC50 value of 200 nM. IRE1α is a dual serine/threonine-protein kinase/endoribonuclease with two enzymatic domains: a trans-autophosphorylation domain and and endoribonuclease (RNase) domain. When activated, usually in response to endoplasmic reticulum (ER) stress such as the unfolded protein response (UPR), IRE1α oligomerizes and activates mRNA splicing of adaptive XBP1 transcription factor, which upregulates ER chaperones and ER associated degradation (ERAD) genes that promote degradation of ER unfolded proteins and facilitate recovery from ER stress. However, if ER stress is too high or chronic, IRE1α is hyperactivated, increasing many ER mRNAs, resulting in apoptosis. GSK2850163 interacts with IRE1α catalytic residues Lys599 and Glu612, displacing the kinase activation loop to the inactive DFG-out conformation. The rearrangement of the kinase domain-dimer interface also results in the RNAse domains rotating away from each other, inhibiting the RNase activity. | [storage]
Store at -20°C | [References]
[1] Nestor O. Concha, et al. Long-Range Inhibitor-Induced Conformational Regulation of Human IRE1α Endoribonuclease Activity. Molecular Pharmacology December 2015, 88 (6) 1011-1023. |
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InvivoChem
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Merck KGaA
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www.sigmaaldrich.cn |
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