9ZUZ
Translation Initiation Factor eIF-2B complex with the Isohexide Diamine GSK735
This is a non-PDB format compatible entry.
Summary for 9ZUZ
| Entry DOI | 10.2210/pdb9zuz/pdb |
| Descriptor | Translation initiation factor eIF-2B subunit alpha, Translation initiation factor eIF-2B subunit beta, Translation initiation factor eIF2B subunit delta, ... (8 entities in total) |
| Functional Keywords | eif2b, integrated stress response, translation |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 114836.62 |
| Authors | |
| Primary citation | Colandrea, V.J.,Joshi-Pangu, A.,Nolte, R.T.,Bledsoe, R.K.,Ward, P.,Glancy, J.,Kowalski, M.D.,Huff, C.A.,Desai, S.,Nagilla, R.,Laping, N.J.,Axten, J.M.,Evans, K.A. Discovery of Isohexide Bisglycolamides as Inhibitors of the Integrated Stress Response. Acs Med.Chem.Lett., 17:495-502, 2026 Cited by PubMed Abstract: 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 (2.25Å) X-ray cocrystal structure of the eIF2B (α,β,δ) complex with compound is reported, which can inform subsequent SAR. PubMed: 41704357DOI: 10.1021/acsmedchemlett.5c00698 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
Download full validation report
