Theme 4 Lecture 15 Flashcards
ALz
What is the role of fragment-based drug discovery in developing a BACE-1 inhibitor?
Involves smaller fragments binding to the target protein, in this case BACE-1 is crucial in alzheimers therapy
Computational
How is virtual screening used for Glycine α1 receptor potentiation?
Uses computational modelling to predict how differenent compounds will react with Glycine a1
What is the significance of BACE-1 in Alzheimer’s disease?
Produces β-amyloid peptides which are implicated in ALz disease, and the production of these in the brain links to alz neuronal cell death.
NMR signals
How is NMR screening used for BACE-1 inhibitors?
NMR screening helps identify compounds that bind to BACE1 by detecting changes in NMR signals.
Bace PRO
How are active fragments for BACE-1 inhibitors identified?
Also identified via NMR however the screening looks at BACE proteins bound with compounds
fret/xray crys
Describe the optimization process of BACE-1 inhibitors.(Isothiourea)
Optimization involves refining initial hits for better efficacy and safety, guided by assays like FRET and X-ray crystallography
CC, PAIN/tra
What is the goal of virtual screening in hGlyR-α1 research?
To find compounds which enhance the function of hGlyR-α1
Which is a chloride channel involved in inhibitory pain and transmission regulation.
FDA
How is the screening plan for Glycine receptor potentiators designed?
Screens vitrual libaray of FDA aprroved drugs against different conformers of the glycine receptor to find potentiators
What do black and colored spots signify in BACE-1 NMR screening?
Black spots represent the BACE protein alone, while colored spots indicate the presence of a compound binding to BACE.
Compound 3,2aminopyyridine and iminohydantoin
What is fragment optimization in BACE-1 inhibitor development?
Look at slide 7
Fragment optimization involves refining a small molecule that binds to BACE-1, like Compound 3. This process uses structure-guided design to create more effective molecules.
Such as the 2-aminopyridine and iminohydantoin lead series, which form strong hydrogen bonds with key active site amino acids (Asp32 and Asp228) in BACE-1.
membrane lipids
How is predicted affinity relevant in drug screening?
Determines how well a drug might act on a target, can be influenced by factors like mebrane lipids.
Xenopus oocytes
What is the significance of potentiation of the Glycine channel in cells?
Xenopus oocytes is a model used to understand how certain drugs can enhance the channel’s function.
lipid ,docking
How is virtual potentiation correlated with actual potentiation in drug discovery?
By the use of docking scores compared virtual and biological models to help validate predicted responses especially with lipid interactions.
