Crystallization (Comment) | Organism |
---|---|
in complex with inhibitor (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5H-spiro[chromeno[2,3-b]pyridine-5,4-oxazol]-2-amine. The aminooxazoline unit engages in hydrogen-bonding interactions with the catalytic aspartic acid residues of the enzyme, and the nitrogen atom of the 2-pyridyl-3-fluoro group interacts with Ser229 via a bridging water molecule in the S3 pocket | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine | inhibitor shows good BACE1 functional potency, permeability, intrinsic stability, and P-glycoprotein efflux ratios | Homo sapiens | |
(S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5H-spiro[chromeno[2,3-b]pyridine-5,4-oxazol]-2-amine | i.e. AMG-8718.compound exhibits a balanced profile of BACE1 potency, hERG binding affinity, and P-glycoprotein recognition. Compound produces robust and sustained reductions of cerebrospinal fluid and brain amyloid beta levels in a rat pharmacodynamic model | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P56817 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
HEK-293 cell | - |
Homo sapiens | - |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000007 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | (S)-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5H-spiro[chromeno[2,3-b]pyridine-5,4-oxazol]-2-amine | |
0.0000009 | - |
pH not specified in the publication, temperature not specified in the publication | Homo sapiens | (S)-3-(6,6-dimethyl-3,6-dihydro-2H-pyran-4-yl)-7-(2-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine |