10.1021/jm048995+.s001
Venkat R. Macherla
Venkat R.
Macherla
Scott S. Mitchell
Scott S.
Mitchell
Rama Rao Manam
Rama Rao
Manam
Katherine A. Reed
Katherine A.
Reed
Ta-Hsiang Chao
Ta-Hsiang
Chao
Benjamin Nicholson
Benjamin
Nicholson
Gordafaried Deyanat-Yazdi
Gordafaried
Deyanat-Yazdi
Bao Mai
Bao
Mai
Paul R. Jensen
Paul R.
Jensen
William F. Fenical
William F.
Fenical
Saskia T. C. Neuteboom
Saskia
T. C. Neuteboom
Kin S. Lam
Kin S.
Lam
Michael A. Palladino
Michael A.
Palladino
Barbara C. M. Potts
Barbara
C. M. Potts
Structure−Activity Relationship Studies
of Salinosporamide A (NPI-0052), a Novel
Marine Derived Proteasome Inhibitor
American Chemical Society
2005
Halogen exchange
insight
chloroethyl group
stereochemical modifications
analogue
Relationship
NF
Marked reductions
activation
assay
relationship
replacement
unhalogenated substituents
finding
cyclohexene ring epoxidation
proteasome inhibition
Novel Marine Derived Proteasome Inhibitor Salinosporamide
cytotoxicity
potency
NPI
attenuated activity
proteasome inhibitor
novel series
2005-06-02 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Structure_Activity_Relationship_Studies_of_Salinosporamide_A_NPI_0052_a_Novel_Marine_Derived_Proteasome_Inhibitor/3373810
Salinosporamide A (<b>1</b>, NPI-0052) is a potent proteasome inhibitor in development for treating cancer. In this
study, a series of analogues was assayed for cytotoxicity,
proteasome inhibition, and inhibition of NF-κB activation.
Marked reductions in potency in cell-based assays accompanied replacement of the chloroethyl group with unhalogenated
substituents. Halogen exchange and cyclohexene ring epoxidation were well tolerated, while some stereochemical modifications significantly attenuated activity. These findings
provide insights into structure−activity relationships within
this novel series.