7T9H
HIV Integrase in complex with Compound-15
Summary for 7T9H
| Entry DOI | 10.2210/pdb7t9h/pdb |
| Descriptor | Integrase, MAGNESIUM ION, (2S)-tert-butoxy[2-methyl-4-(4-methylphenyl)quinolin-3-yl]acetic acid, ... (4 entities in total) |
| Functional Keywords | dna integration, aids, rnaseh, ledgf, endonuclease, hiv-1 integrase, dna binding protein, viral protein |
| Biological source | Human immunodeficiency virus 1 |
| Total number of polymer chains | 2 |
| Total formula weight | 37018.71 |
| Authors | Khan, J.A.,Lewis, H.,Kish, K. (deposition date: 2021-12-19, release date: 2022-04-06, Last modification date: 2023-10-18) |
| Primary citation | Naidu, B.N.,Patel, M.,McAuliffe, B.,Ding, B.,Cianci, C.,Simmermacher, J.,Jenkins, S.,Parker, D.D.,Sivaprakasam, P.,Khan, J.A.,Kish, K.,Lewis, H.,Hanumegowda, U.,Krystal, M.,Meanwell, N.A.,Kadow, J.F. Design, Synthesis, and Preclinical Profiling of GSK3739936 (BMS-986180), an Allosteric Inhibitor of HIV-1 Integrase with Broad-Spectrum Activity toward 124/125 Polymorphs. J.Med.Chem., 65:4949-4971, 2022 Cited by PubMed Abstract: Allosteric HIV-1 integrase inhibitors (ALLINIs) have garnered special interest because of their novel mechanism of action: they inhibit HIV-1 replication by promoting aberrant integrase multimerization, leading to the production of replication-deficient viral particles. The binding site of ALLINIs is in a well-defined pocket formed at the interface of two integrase monomers that is characterized by conserved residues along with two polymorphic amino acids at residues 124 and 125. The design, synthesis, and optimization of pyridine-based allosteric integrase inhibitors are reported here. Optimization was conducted with a specific emphasis on the inhibition of the 124/125 polymorphs such that the designed compounds showed excellent potency against majority of the 124/125 variants. profiling of promising preclinical lead showed that it exhibited a good pharmacokinetic (PK) profile in preclinical species, which resulted in a low predicted human efficacious dose. However, findings in rat toxicology studies precluded further development of . PubMed: 35235334DOI: 10.1021/acs.jmedchem.1c02169 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.53 Å) |
Structure validation
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