5C25

Crystal Structure of HIV-1 Reverse Transcriptase in Complex with 6-((4-((4-cyanophenyl)amino)-1,3,5-triazin-2-yl)amino)-5,7-dimethyl-2-naphthonitrile (JLJ639), a Non-nucleoside Inhibitor

Summary for 5C25

• Entry DOI: 10.2210/pdb5c25/pdb
• Related: 4KKO 4MFB 4O44 4O4G 5C24
• Descriptor: HIV-1 REVERSE TRANSCRIPTASE, P66 SUBUNIT, HIV-1 REVERSE TRANSCRIPTASE, P51 SUBUNIT, 6-({4-[(4-cyanophenyl)amino]-1,3,5-triazin-2-yl}amino)-5,7- dimethyl-2-naphthonitrile, ... (6 entities in total)
• Functional Keywords: polymerase, reverse transcriptase, hiv, non-nucleoside inhibitor, transferase, hydrolase-dna-inhibitor complex, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Human immunodeficiency virus type 1 group M subtype B (isolate BH10) (HIV-1); More
• Total number of polymer chains: 2
• Total formula weight: 114636.58

Authors

Chan, A.H.,Frey, K.M.,Anderson, K.S. (deposition date: 2015-06-15, release date: 2015-07-29, Last modification date: 2023-09-27)

Primary citation

Lee, W.G.,Frey, K.M.,Gallardo-Macias, R.,Spasov, K.A.,Chan, A.H.,Anderson, K.S.,Jorgensen, W.L.
Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase.
Bioorg.Med.Chem.Lett., 25:4824-4827, 2015

PubMed Abstract: Non-nucleoside inhibitors of HIV-1 reverse transcriptase (HIV-RT) are reported that incorporate a 7-indolizinylamino or 2-naphthylamino substituent on a pyrimidine or 1,3,5-triazine core. The most potent compounds show below 10 nanomolar activity towards wild-type HIV-1 and variants bearing Tyr181Cys and Lys103Asn/Tyr181Cys resistance mutations. The compounds also feature good aqueous solubility. Crystal structures for two complexes enhance the analysis of the structure-activity data.

PubMed: 26166629
DOI: 10.1016/j.bmcl.2015.06.074

Experimental method

X-RAY DIFFRACTION (2.841 Å)