BMS-933043, a Selective α7 nAChR Partial Agonist for the Treatment of Cognitive Deficits Associated with Schizophrenia.
The therapeutic treatment of negative symptoms and cognitive dysfunction associated with schizophrenia is a significant unmet medical need. Preclinical literature indicates that α7 neuronal nicotinic acetylcholine (nACh) receptor agonists may provide an effective approach to treating cognitive dysfunction in schizophrenia. We report herein the discovery and evaluation of1c(BMS-933043), a novel and potent α7 nACh receptor partial agonist with high selectivity against other nicotinic acetylcholine receptor subtypes (>100-fold) and the 5-HT3Areceptor (>300-fold).In vivoactivity was demonstrated in a preclinical model of cognitive impairment, mouse novel object recognition. BMS-933043 has completed Phase I clinical trials.
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Dalton
D
King
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Christiana
C
Iwuagwu
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Jim
J
Cook
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Ivar M
IM
McDonald
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Robert
R
Mate
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
F Christopher
FC
Zusi
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Matthew D
MD
Hill
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Haiquan
H
Fang
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Rulin
R
Zhao
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Bei
B
Wang
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Amy E
AE
Easton
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Regina
R
Miller
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Debra
D
Post-Munson
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Ronald J
RJ
Knox
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Lizbeth
L
Gallagher
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Ryan
R
Westphal
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Thaddeus
T
Molski
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Jingsong
J
Fan
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Wendy
W
Clarke
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Yulia
Y
Benitex
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Kimberley A
KA
Lentz
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Rex
R
Denton
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Daniel
D
Morgan
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Robert
R
Zaczek
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Nicholas J
NJ
Lodge
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Linda J
LJ
Bristow
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
John E
JE
Macor
Research and Development, Bristol-Myers Squibb , 5 Research Parkway, Wallingford, Connecticut 06492, United States.
Richard E
RE
Olson
Schizophrenia; clinical candidate; quinuclidine; α7 nAChR partial agonist; α7 neuronal nicotinic acetylcholine receptor