J
James Fleming
Researcher at Pfizer
Publications - 6
Citations - 1071
James Fleming is an academic researcher from Pfizer. The author has contributed to research in topics: Transthyretin & Tafamidis. The author has an hindex of 6, co-authored 6 publications receiving 939 citations. Previous affiliations of James Fleming include Massachusetts Institute of Technology & Millennium Pharmaceuticals.
Papers
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Journal ArticleDOI
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade
Christine Bulawa,Stephen Connelly,Michael Devit,Lan Wang,Charlotte Weigel,James Fleming,Jeff Packman,Evan T. Powers,R. Luke Wiseman,Ted R. Foss,Ian A. Wilson,Jeffery W. Kelly,Richard Labaudinière +12 more
TL;DR: The molecular and structural basis of TTR tetramer stabilization by tafamidis is described, suggesting that binding stabilizes the weaker dimer-dimer interface against dissociation, the rate-limiting step of amyloidogenesis.
Journal ArticleDOI
Complementary whole-genome technologies reveal the cellular response to proteasome inhibition by PS-341.
James Fleming,Eric S. Lightcap,Seth Sadis,Vala Thoroddsen,Christine E. Bulawa,Ronald K. Blackman +5 more
TL;DR: This study has used two whole-genome technologies in Saccharomyces cerevisiae to determine the cellular impact of the proteasome inhibitor PS-341 and identified Rpn4p as the transcription factor most responsible for the cell's ability to compensate for proteasomes inhibition.
Journal ArticleDOI
Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transthyretin Amyloidosis
Teresa Coelho,Giampaolo Merlini,Christine Bulawa,James Fleming,Daniel P. Judge,Jeffery W. Kelly,Mathew S. Maurer,Violaine Planté-Bordeneuve,Richard Labaudinière,Rajiv Mundayat,Steve Riley,Ilise Lombardo,Pedro E. Huertas +12 more
TL;DR: Tafamidis meglumine is a rationally designed, non-NSAID benzoxazole derivative that binds with high affinity and selectivity to TTR and kinetically stabilizes the tetramer, slowing monomer formation, misfolding, and amyloidogenesis.
Patent
Inhibition of alpha-synuclein toxicity
Susan Lindquist,Tiago F. Outeiro,Richard Labaudinière,James Fleming,Christine E. Bulawa,Charlotte Weigel,Feng Liang,Sandeep K. Gupta,Amy Ripka +8 more
TL;DR: In this paper, compounds and compositions are provided for treatment or amelioration of one or more symptoms of α-synuclein toxicity, α-synuclein mediated diseases or diseases in which α-nuclein fibrils are a symptom or cause of the disease.
Journal Article
Biological characterization of MLN944: A potent DNA binding agent
Darshan S. Sappal,A. Kathleen McClendon,James Fleming,Vala Thoroddsen,Kelly Connolly,Corinne Reimer,Ronald K. Blackman,Christine E. Bulawa,Neil Osheroff,Peter Charlton,Laura A Rudolph-Owen +10 more
TL;DR: It is shown that MLN 944 intercalates into DNA, but has no effect on the catalytic activity of either topoisomerase I or II, suggesting that the primary mechanism of action of MLN944 likely involves DNA binding and intercalation, but does not appear to involve topoisomersase inhibition.