ORIGINAL ARTICLEFirst small-molecule PROTACs for G protein-coupled receptors: inducing α1A-adrenergic receptor degradation
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Graphical abstract
Small-molecule proteolysis targeting chimeras (PROTACs) of α1A-adrenergic receptor (α1A-AR) were designed and synthesized through conjugation of known α1-ARs inhibitor prazosin and CRBN ligand pomalidomide through different linkers. Selected compounds displayed remarkable degradation activity. Inhibition of PC-3 cells proliferation and tumor growth regression of these compounds were investigated.
Key words
Small-molecule PROTACs
α1A-Adrenergic receptor
Ubiquitylation
Degradation
Prostate cancer
Abbreviations
α1-ARs
α1-adrenergic receptors
α1A-AR
α1A-adrenergic receptor
α1B-AR
α1B-adrenergic receptor
α1D-AR
α1D-adrenergic receptor
BPH
benign prostatic hyperplasia
CRBN
cereblon
DCM
dichloromethane
DMF
dimethylformamide
DMSO
dimethylsulfoxide
GPCR
G-protein-coupled receptor
hPCE
human prostate cancer epithelial
HPLC
high-performance liquid chromatography
LUTS
lower urinary tract symptoms
PROTACs
proteolysis targeting chimeras
TEA
triethylamine
THF
tetrahydrofuran
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