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@ARTICLE{Bi:626512,
author = {Bi, Chunyang and Mirza, Salahuddin and Baburi, Helay and
Schäkel, Laura and Winzer, Riekje and Moschütz, Susanne
and Keetz, Kilian and Lopez, Vittoria and Pelletier, Julie
and Sévigny, Jean and Schulze zur Wiesch, Julian and Claff,
Tobias and Tolosa, Eva and Namasivayam, Vigneshwaran and
Straeter, Norbert and Müller, Christa E.},
title = {{S}ynthesis, {C}haracterization, {I}nteractions, and
{I}mmunomodulatory {F}unction of {E}ctonucleotidase
{CD}39/{CD}73 {I}nhibitor 8-{B}utylthioadenosine
5′-{M}onophosphate},
journal = {ACS pharmacology $\&$ translational science},
volume = {8},
number = {5},
issn = {2575-9108},
address = {Washington, DC},
publisher = {ACS Publications},
reportid = {PUBDB-2025-01465},
pages = {1401 - 1415},
year = {2025},
note = {waiting for fulltext},
abstract = {Ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1,
CD39) catalyzes the extracellular hydrolysis of ATP
generating AMP, while ecto-5′-nucleotidase (CD73) further
hydrolyzes AMP yielding immunosuppressive adenosine.
8-Butylthioadenosine 5′-monophosphate (8-BuS-AMP) was
described as a CD39 inhibitor but has been poorly
characterized. The standard CD39 antagonist ARL 67156 is not
suitable for in vivo studies due to metabolic instability.
In the present study, we optimized and upscaled the
synthesis of 8-BuS-AMP and performed a comprehensive
investigation of its properties. It behaves as a competitive
inhibitor at human and mouse CD39, and additionally inhibits
CD73. Docking studies using a homology model of human CD39
and determination of an atomic-resolution (1.06 Å)
cocrystal structure with human CD73 indicated the
inhibitor’s interactions within the substrate binding
pockets and explained the compound’s stability toward
hydrolysis. 8-BuS-AMP is metabolically highly stable in
human and mouse liver microsomes. It inhibited ε-adenosine
formation from ε-ATP and ε-AMP in human synovial fluid and
enhanced activation and proliferation of peripheral human T
lymphocytes. Thus, 8-BuS-AMP is a recommended tool compound
for studying purinergic signaling in vitro and in vivo,
being superior to the standard CD39 inhibitor ARL 67156.
Moreover, it may serve as a lead structure to develop drugs
for the immunotherapy of cancer.},
cin = {EMBL-User},
ddc = {610},
cid = {I:(DE-H253)EMBL-User-20120814},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project
G:(GEPRIS)335447717 - SFB 1328: Adeninnukleotide in
Immunität und Entzündung (335447717)},
pid = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)335447717},
experiment = {EXP:(DE-H253)P-P14-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {40370983},
UT = {WOS:001458665100001},
doi = {10.1021/acsptsci.5c00126},
url = {https://bib-pubdb1.desy.de/record/626512},
}