4nyf

HIV integrase in complex with inhibitorHIV integrase in complex with inhibitor

Structural highlights 4nyf is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed An assay recapitulating the 3' processing activity of HIV-1 integrase (IN) was used to screen the Boehringer Ingelheim compound collection. Hit-to-lead and lead optimization beginning with compound 1 established the importance of the C3 and C4 substituent to antiviral potency against viruses with different aa124/aa125 variants of IN. The importance of the C7 position on the serum shifted potency was established. Introduction of a quinoline substituent at the C4 position provided a balance of potency and metabolic stability. Combination of these findings ultimately led to the discovery of compound 26 (BI 224436), the first NCINI to advance into a phase Ia clinical trial. Discovery of BI 224436, a Noncatalytic Site Integrase Inhibitor (NCINI) of HIV-1.,Fader LD, Malenfant E, Parisien M, Carson R, Bilodeau F, Landry S, Pesant M, Brochu C, Morin S, Chabot C, Halmos T, Bousquet Y, Bailey MD, Kawai SH, Coulombe R, LaPlante S, Jakalian A, Bhardwaj PK, Wernic D, Schroeder P, Amad M, Edwards P, Garneau M, Duan J, Cordingley M, Bethell R, Mason SW, Bos M, Bonneau P, Poupart MA, Faucher AM, Simoneau B, Fenwick C, Yoakim C, Tsantrizos Y ACS Med Chem Lett. 2014 Jan 22;5(4):422-7. doi: 10.1021/ml500002n. eCollection, 2014 Apr 10. PMID:24900852 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4nyf, resolution 1.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image