9zuz

Translation Initiation Factor eIF-2B complex with the Isohexide Diamine GSK735

spinqualitylabelsall models 9zuz, resolution 2.25Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9zuz is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.25Å Ligands: A1C32, EDO, PRO, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease EI2BA_HUMAN Cree leukoencephalopathy;Late infantile CACH syndrome;Ovarioleukodystrophy. The disease is caused by mutations affecting the gene represented in this entry. Function EI2BA_HUMAN Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. Publication Abstract from PubMed ISRIB reactivates protein synthesis for cells under stress through the stabilization of eukaryotic initiation factor 2 beta (eIF2B). We discovered that diaminoisohexides, derived from isomannide and isosorbide serve as a bioisostere for the diamino cyclohexane core in ISRIB. These scaffolds conferred improved solubility but also showed activity for the human ether-a-go-go-related gene (hERG). Herein we describe our efforts to mitigate hERG activity while maintaining target potency. The first high resolution (2.25A) X-ray cocrystal structure of the eIF2B (alpha,beta,delta)(2) complex with compound 7a is reported, which can inform subsequent SAR. Discovery of Isohexide Bisglycolamides as Inhibitors of the Integrated Stress Response.,Colandrea VJ, Joshi-Pangu A, Nolte RT, Bledsoe RK, Ward P, Glancy J, Kowalski MD, Huff CA, Desai S, Nagilla R, Laping NJ, Axten JM, Evans KA ACS Med Chem Lett. 2026 Jan 15;17(2):495-502. doi: , 10.1021/acsmedchemlett.5c00698. eCollection 2026 Feb 12. PMID:41704357 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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