Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.21.73 (
urokinase-type plasminogen activator
)
10,685
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Fragment-based drug discovery (FBDD) has evolved into an established approach for "hit" identification. Typically, most applications of FBDD depend on specialised cost- and time-intensive biophysical techniques. The substrate activity screening (SAS) approach has been proposed as a relatively cheap and straightforward alternative for identification of fragments for enzyme inhibitors. We have investigated SAS for the discovery of inhibitors of oncology target
urokinase
(
uPA
). Although our results support the key hypotheses of SAS, we also encountered a number of unreported limitations. In response, we propose an efficient modified methodology: "MSAS" (modified substrate activity screening).
MSAS
circumvents the limitations of SAS and broadens its scope by providing additional fragments and more coherent SAR data. As well as presenting and validating
MSAS
, this study expands existing SAR knowledge for the S1 pocket of
uPA
and reports new reversible and irreversible
uPA
inhibitor scaffolds.
...
PMID:Repositioning the substrate activity screening (SAS) approach as a fragment-based method for identification of weak binders. 2515 78
