5KGW

HIV1 catalytic core domain in complex with inhibitor: (2~{S})-2-[3-(3,4-dihydro-2~{H}-chromen-6-yl)-1-methyl-indol-2-yl]-2-[(2-methylpropan-2-yl)oxy]ethanoic acid

Summary for 5KGW

• Entry DOI: 10.2210/pdb5kgw/pdb
• Descriptor: Integrase, SULFATE ION, (2S)-tert-butoxy[3-(3,4-dihydro-2H-1-benzopyran-6-yl)-1-methyl-1H-indol-2-yl]acetic acid, ... (4 entities in total)
• Functional Keywords: integrase allini nucleic acid binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 18834.11

Authors

Feng, L.,Kobe, M.,Kvaratskhelia, M. (deposition date: 2016-06-13, release date: 2016-10-19, Last modification date: 2024-11-20)

Primary citation

Patel, P.A.,Kvaratskhelia, N.,Mansour, Y.,Antwi, J.,Feng, L.,Koneru, P.,Kobe, M.J.,Jena, N.,Shi, G.,Mohamed, M.S.,Li, C.,Kessl, J.J.,Fuchs, J.R.
Indole-based allosteric inhibitors of HIV-1 integrase.
Bioorg.Med.Chem.Lett., 26:4748-4752, 2016

PubMed Abstract: Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.

PubMed: 27568085
DOI: 10.1016/j.bmcl.2016.08.037

Experimental method

X-RAY DIFFRACTION (2.34 Å)