Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms.
JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Honghe
H
Wan
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Gretchen M
GM
Schroeder
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Amy C
AC
Hart
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Jennifer
J
Inghrim
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
James
J
Grebinski
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
John S
JS
Tokarski
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Matthew V
MV
Lorenzi
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Dan
D
You
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Theresa
T
Mcdevitt
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Becky
B
Penhallow
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Ragini
R
Vuppugalla
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Yueping
Y
Zhang
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Xiaomei
X
Gu
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Ramaswamy
R
Iyer
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Louis J
LJ
Lombardo
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
George L
GL
Trainor
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Stefan
S
Ruepp
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Jonathan
J
Lippy
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Yuval
Y
Blat
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
John S
JS
Sack
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Javed A
JA
Khan
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Kevin
K
Stefanski
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Bogdan
B
Sleczka
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Arvind
A
Mathur
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Jung-Hui
JH
Sun
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Michael K
MK
Wong
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Dauh-Rurng
DR
Wu
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Peng
P
Li
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Anuradha
A
Gupta
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
P N
PN
Arunachalam
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Bala
B
Pragalathan
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Sankara
S
Narayanan
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Nanjundaswamy
N
K C
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Prakasam
P
Kuppusamy
Bristol-Myers Squibb R&D , US Route 206 and Province Line Road, Princeton, New Jersey 08543-4000, United States.
Ashok V
AV
Purandare
BMS-911543; JAK2; myeloproliferative neoplasm; selective inhibitor; structure-guided design