5U6E
Crystal structure of clade A/E HIV-1 gp120 core in complex with NBD-14010
Summary for 5U6E
| Entry DOI | 10.2210/pdb5u6e/pdb |
| Descriptor | clade A/E 93TH057 HIV-1 gp120 core, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-{(1S)-2-amino-1-[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]ethyl}-5-(4-chloro-3-fluorophenyl)-1H-pyrrole-2-carboxamide, ... (5 entities in total) |
| Functional Keywords | hiv-1, nbd-14010, virus entry antagonist, small molecule, viral protein |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 83596.84 |
| Authors | Kwon, Y.D.,Debnath, A.K.,Kwong, P.D. (deposition date: 2016-12-07, release date: 2017-03-22, Last modification date: 2024-10-30) |
| Primary citation | Curreli, F.,Kwon, Y.D.,Belov, D.S.,Ramesh, R.R.,Kurkin, A.V.,Altieri, A.,Kwong, P.D.,Debnath, A.K. Synthesis, Antiviral Potency, in Vitro ADMET, and X-ray Structure of Potent CD4 Mimics as Entry Inhibitors That Target the Phe43 Cavity of HIV-1 gp120. J. Med. Chem., 60:3124-3153, 2017 Cited by PubMed Abstract: In our attempt to optimize the lead HIV-1 entry antagonist, NBD-11021, we present in this study the rational design and synthesis of 60 new analogues and determination of their antiviral activity in a single-cycle and a multicycle infection assay to derive a comprehensive structure-activity relationship (SAR). Two of these compounds, NBD-14088 and NBD-14107, showed significant improvement in antiviral activity compared to the lead entry antagonist in a single-cycle assay against a large panel of Env-pseudotyped viruses. The X-ray structure of a similar compound, NBD-14010, confirmed the binding mode of the newly designed compounds. The in vitro ADMET profiles of these compounds are comparable to that of the most potent attachment inhibitor BMS-626529, a prodrug of which is currently undergoing phase III clinical trials. The systematic study presented here is expected to pave the way for improving the potency, toxicity, and ADMET profile of this series of compounds with the potential to be moved to the early preclinical development. PubMed: 28266845DOI: 10.1021/acs.jmedchem.7b00179 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.095 Å) |
Structure validation
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