AMG-8718

Ligand id: 9639

Name: AMG-8718

Structure and Physico-chemical Properties

2D Structure
Calculated Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 1
Topological polar surface area 91.85
Molecular weight 442.14
XLogP 3.14
No. Lipinski's rules broken 0

Molecular properties generated using the CDK

Classification
Compound class Synthetic organic
Database Links
PubChem CID 45254510
Search Google for chemical match using the InChIKey GKKFBOARESVMBW-VWLOTQADSA-N
Search Google for chemicals with the same backbone GKKFBOARESVMBW
Search UniChem for chemical match using the InChIKey GKKFBOARESVMBW-VWLOTQADSA-N
Search UniChem for chemicals with the same backbone GKKFBOARESVMBW
Comments
This Amgen BACE1 inhibitor for Alzheimer's disease, AMG-8718, had a balanced profile of potency, hERG binding affinity, and Pgp recognition. It also produced robust and sustained reductions of CSF and brain Aβ levels in a rat pharmacodynamic model [1]. However, retinal thinning was observed in a 1-month toxicity study in the rat and further studies suggested this to be an off-target effect where, in the rat, AMG-8718 impairs phagolysosomal function, leading to photoreceptor dysfunction and ultimately loss of photoreceptors [2]. The compound is example 288 in [3] from over 1000 analogues, but only binned activity data is provided. While the PubChem Bioassay data and other sources link to this structure note that MMDB and PubMed link their PDB structure to a different tautomeric representation as PubChem CID 86580376.