Lovering, F*.; Morgan,
P.; Allais, C.; Aulabaugh, A; Brodfuehrer, J.; Chang, J; Coe, J.;
Ding, W.; Dowty, H.; Fleming, M.; Frisbie, R.; Guzova, J.; Hepworth, D.; Jasti,
J.; Kortum, S.; Kurumbail, R.; Mohan, S.; Papaioannou, N.; Strohbach, J. W.;
Vincent, F.; Lee, K.; Zapf, C. W.; Rational Approach to Highly
Potent and Selective Apoptosis Signal-Regulating Kinase 1 (ASK1)
inhibitors. Eur. J. Med. Chem. 2018, 145,
606-621.
K.L. Lee*, C.M. Ambler, D.R. Anderson, B.P. Boscoe, A.G. Bree, J.I.
Brodfuehrer, J.S. Chang, C. Choi, S. Chung, K.J. Curran, J.E.
Day, C.M. Dehnhardt, K. Dower, S.E. Drozda, R.K. Frisbie, L.K.
Gavrin, J.A. Goldberg, S. Han, M. Hegen, D.Hepworth, H.R. Hope, S. Kamtekar,
I.C. Kilty, A. Lee, L.-L. Lin, F.E. Lovering, M.D. Lowe, J.P.
Mathias, H.M. Morgan, E.A. Murphy, N. Papaioannou, A. Patny, B.S. Pierce, V.R.
Rao, E. Saiah, I.J. Samardjiev, B.M. Samas, M.W.H. Shen, J.H.
Shin, H.H. Soutter, J.W. Strohbach, P.T. Symanowicz, J.R. Thomason, J.D.
Trzupek, R. Vargas, F. Vincent, J. Yan, C.W. Zapf, and S.W. Wright*,
“Discovery of clinical candidate
1-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide
(PF-06650833), a potent, selective inhibitor of interleukin-1 receptor
associated kinase 4 (IRAK4), by fragment-based drug design.” J. Med.
Chem. 2017, 5521-5542.
S. Vollmer, T. Zhang, N.
Gray, K. Lee, V. Rao, and P. Cohen, "The mechanism of
activation of IRAK1 and IRAK4 by interleukin-1 and Toll-Like receptor
agonists." Biochemical Journal, 2017, 474,
2027-2038.
L. Cushing, A. Winkler,
S. Jelinsky, K. Lee, W. Krouver, R. Hatwin, V.R. Rao, M. Fleming,
L.-L. Lin, “IRAK4 kinase activity mediates IRF5 activation via IKKb and TAK1.” J.
Biol. Chem. 2017, doi: 10.1074/jbc.M117.796912.
P. Thakker, S. Marusic,
N.L. Stedman, K.L. Lee, J.C. McKew, A. Wood, S.J. Goldman, M.W.
Leach, M. Collins, V.K. Kuchroo, S.F. Wolf, J.D. Clark, M. Hassan-Zahraee,
“Cytosolic phospholipase A2a blockade abrogates disease during the tissue-damage effector
phase of experimental autoimmune encephalomyelitis by its action on
APCs.” J. Immunol., 2011, 187(4), 1986-1997.
C.L. Nickerson-Nutter,
D. Goodwin, M.W.H. Shen, C. Damphousse, W. Duan, T.A. Samad, J.C. McKew, K.L.
Lee, M.M. Zaleska, N. Mollova, J.D. Clark, “The cPLA2a inhibitor
Efipladib decreases nociceptive responses without affecting PGE2 levels in the
cerebral spinal fluid.” Neuropharmacology, 2011, 60,
633-641.
L. Chen*, W.
Wang, K.L. Lee, M.W.H. Shen, J.L. Wu, E.A. Murphy, W. Zhang, X. Xu,
S. Tam, C. Nickerson-Nutter, D.G. Goodwin, J.D. Clark, and J.C.
McKew, “Reactions of functionalized sulfonamides: Application to lowering the
lipophilicity of cPLA2a inhibitors.” J.
Med. Chem., 2009, 52, 1156-1171.
S. Marusic*, P.
Thakker*, J. W.; Pelker, N. Stedman, K.L. Lee, J.C. McKew, L. Han,
X. Xu, S.F. Wolf, A.J. Borey, J. Cui, M. W. Shen, F. Donahue, M. Hassan-Zahree,
M.W. Leach, T. Shimizu, J.D. Clark, “Selective blockade of cytosolic
phospholipase A2a prevents experimental autoimmune encephalomyelitis and
diminishes development of Th1 and Th17 responses in mice.” Journal of
Neuroimmunology, 2008, 204, 29-37.
M.K. Ramarao*,
M. Shen, E. Murphy, W. Duan, Y. Zhao, J. McKew, K.L. Lee, P.
Thakker, M.L. Behnke, and J.D. Clark*, “Thermodynamic
characterization of cPLA2a inhibitors.” Analytical
Biochemistry, 2008, 383, 217-225.
J.C. McKew*, K.L.
Lee, M.W.H. Shen, P. Thakker, M.A. Foley, M.L. Behnke, B. Hu, F.-W. Sum, S.
Tam, Y. Hu, L. Chen, S.J. Kirincich, R. Michalak, J. T.on, M. Ipek, K.
Wu, L. Wooder, M.K. Ramarao, E.A. Murphy, D.G. Goodwin, L. Albert, X. Xu,
F. Donahue, M.S. Ku, J. Keith, C.L. Nickerson-Nutter, W. M.
Abraham, C. Williams, M. Hegen, and J.D. Clark, “Indole cPLA2a inhibitors:
Discovery and in vitro and in vivo characterization of Efipladib and
WAY-196025.” J. Med. Chem., 2008, 51,
3388-3413.
K.L. Lee*, M.L. Behnke, M.A. Foley, L. Chen, W. Wang, R. Vargas, J. Nunez,
S. Tam, N. Mollova, X. Xu, M.W.H. Shen, M. K. Ramarao, D.G. Goodwin, C.L.
Nickerson-Nutter, C. Williams, W.M. Abraham, J.D. Clark, and
J.C. McKew, “Benzenesulfonamide indole inhibitors of cytosolic phospholipase A2a: Optimization of in
vitro potency and rat pharmacokinetics for oral efficacy.” Bioorg.
Med. Chem., 2008, 16, 1345-1358.
K.L. Lee*; M.A. Foley, L. Chen, M.L. Behnke, F.E. Lovering, S.J.
Kirincich, J. Shim, S.Tam, M.W.H. Shen, S. Khor, X. Xu, D.G. Goodwin, M.K.
Ramarao, C. Nickerson-Nutter, F. Donahue, M.S. Ku, J.D. Clark, and J.C. McKew,
“Discovery of Ecopladib, an indole inhibitor of cytosolic phospholipase A2a.” J. Med. Chem. 2007, 50,
1380-1400.
K.L. Lee, J.B. Goh, S.F. Martin, “Novel entry to the Ergot alkaloids via
ring closing metathesis.” Tetrahedron Letters 2001, 42(9),
1635-1638.
K.M.
Shea, K.L. Lee, R.L. Danheiser, “Synthesis
and properties of 9-alkyl- and 9-arylcyclopenta[a]phenalenes.” Organic
Letters 2000, 2(15), 2353-2356.
K.L. Lee and R.L. Danheiser, “(Trimethylsilyl)allene.” Encyclopedia
of Reagents for Organic Synthesis, 2001.
K.L. Lee and R.L. Danheiser,
“1-Methyl-1-(trimethylsilyl)allene.” Encyclopedia of Reagents for
Organic Synthesis, 2001.
SELECTED PATENTS AND
PATENT APPLICATIONS
J.D. Trzupek, K.L.
Lee, M.E.Bunnage, S.Han, D. Hepworth, F.E. Lovering, J.P. Mathias, N. Papaioannou,
J.W. Strohbach, S.W. Wright, C.W. Zapf, L.K. Gavrin, A. Lee, D.R. Anderson,
C.M. Dehnhardt, E. Saiah, J.A. Goldberg, X. Wang, H.-C. Huang, R. Vargas, M.E.
Lowe, A. Patny, “Bicyclic-fused heteroaryl or aryl compounds” U.S. Patent
10,793,579 B2, Oct. 6, 2020.
K.L. Lee, C.P. Allais, C.M. Dehnhardt, L.K. Gavrin, S. Han, D. Hepworth,
A. Lee, F.E. Lovering, J.M. Mathias, D.R. Owen, N. Papaioannou, E. Saiah, J.W.
Strohbach, J.E. Trzupek, S.W. Wright, C.W. Zapf, “Bicyclic-fused heteroaryl or
aryl compounds are IRAK4 modulators,” WO2017/033093 A1, Mar. 2, 2017.
J.D. Trzupek, K.L.
Lee, M.E.Bunnage, S.Han, D. Hepworth, F.E. Lovering, J.P. Mathias, N.
Papaioannou, J.W. Strohbach, S.W. Wright, C.W. Zapf, L.K. Gavrin, A. Lee, K.J.
Curran, C.M. Dehnhardt, E. Saiah, J.A. Goldberg, X. Wang, R. Vargas, M.E. Lowe,
A. Patny, “Bicyclic-fused heteroaryl or aryl compounds”, U.S. Patent 9,458,168
B2, Oct. 4, 2016.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu,
J.D. Clark, W. Li, V. Clerin, S. Marusic, K. Pong, “Methods for the use of
inhibitors of cytosolic phospholipase A2,” U.S. Patent 7,906,548 B2,
Mar. 15, 2011.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu, J.D.
Clark, “Methods for treating asthmatic conditions,” U.S. Patent 7,713,964 B2,
May 11, 2010.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu,
J.D. Clark, W. Li, V. Clerin, S. Marusic, K. Pong, “Methods for the use of
inhibitors of cytosolic phospholipase A2,” U.S. Patent 7,605,156 B2,
Oct. 20, 2009.
J.C. McKew, K.L.
Lee, L. Chen, R. Vargas, J.D. Clark,C. Williams, V. Clerin, S. Marusic, K.
Pong, “Inhibitors of cytosolic phospholipase A2,” U.S. Patent
7,557,135 B2, July 7, 2009.
J. Xiang, E. Saiah, S.
Tam, J. McKew, L. Chen, M. Donnelly, M. Ipek, K. Lee, H.-Q. Li, J.
Li, W. Li, H.-G. Lombart, J. Nunez, T. Mansour, V. Suri, R. Vargas, C. Wu,
Z.-K. Wan, J. Lee, E. Binnun, D. Wilson, “Sulfonylated piperidine and
piperazine derivatives as 11-b HSD1 inhibitors and their preparation, pharmaceutical
compositions and use in the treatment of diseases,” WO 2007 092435 A2, Aug. 16,
2007.
J.C. McKew, K.
L. Lee, L. Chen, R. Vargas, J.D. Clark, C. Williams, V. Clerin, S. Marusic,
K. Pong, “Indole derivatives as inhibitors of cytosolic phospholipase A2 and
their preparation, pharmaceutical compositions, and use in the prevention and
treatment of various diseases,” WO 2006 128142 A2, Nov. 30, 2006.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu,
J.D. Clark, “Methods for treating arthritic disorders.” U.S. Patent 7,101,875
B2, Sep. 5, 2006.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B.
Hu, J.D. Clark, W. Li, Wei, “Process for making an aldehyde.” U.S. Patent
6,984,735 B2, Jan. 10, 2006.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu,
J.D. Clark, “Inhibitors of cytosolic phospholipase A2,” U.S. Patent
6,797,708 B2, Sept. 28, 2004.
J.C. McKew, S.Y.
Tam, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M. Behnke, B. Hu,
J.D. Clark, “N-Benzhydryl indole compounds,” U.S. Patent 6,635,771 B2, Oct. 21,
2003.
J.C. McKew, S.Y.-K. Tam,
J.D. Clark, K.L. Lee, L. Chen, P. Thakker, F.-W. Sum, M.L. Behnke,
B. Hu, “Inhibitors of cytosolic phospholipase A2,” WO 0348122 A2,
Jun. 12, 2003.
M.E. Langer, F.
Khorshahi, K. Lee, J.F. Hessel, D. Sinfield, “Compositions
containing water-dispersible copolymers of UVA and UVB light-absorbing
monomers,” WO 9322413 A1, Nov. 11, 1993.
M.E. Langer, F.
Khorshahi, K. Lee, “Water-dispersible copolymer containing UVA and
UVB light-absorbing monomers,” U.S. Patent 5,243,021, Sept. 7, 1993.
SELECTED PRESENTATIONS
K.L. Lee and S.W. Wright, “A little molecule grows up: Discovery of an IRAK4 clinical candidate”, US National Chemistry Olympiad Training Camp, invited speakers, June 2, 2021.
K.L. Lee, “Perspectives from an Asian American scientist in the pharmaceutical industry”, USDA Southern Regional Research Center, invited speaker, May 27, 2021.
K.L. Lee, “Celebrating Asian-American Pacific Islander Heritage Month: Who Am I?”, American Chemical Society Staff Webinar, invited speaker, February 10, 2021.
K.L. Lee, “A
medicinal chemistry story, and some free career advice”, Colorado College,
invited speaker, February 10, 2021.
K.L. Lee, “Hindsight
is 20/20: A career in medicinal chemistry”, Hobart and William Smith Colleges,
invited speaker, November 11, 2020.
K.L. Lee, “Hindsight
is 20/20: A career in medicinal chemistry”, Central Massachusetts Local Section
of the American Chemical Society, invited speaker, October 12, 2020.
K.L. Lee, “The
journey to IRAK4 candidate PF-06650833”, Applied Pharmaceutical Chemistry
webinar symposium, invited speaker, October 6, 2020.
K.L. Lee, B.L.
Hoffman, V. Gigi, L. Ruschau, “Breaking through the glass ceiling – advice,
ideas and shared experiences from experienced leaders in healthcare and
pharma”, 5th Annual Advancing Women’s Leadership Skills &
Opportunities in Pharma & Healthcare – East Coast, virtual meeting,
September 23, 2020.
K.L. Lee, “The
journey to IRAK4 candidate PF-06650833”, Peking University-Pfizer Emerging
Science Seminar Series, Peking University, Peking, China, June 12, 2020.
K.L. Lee, “What
the ACS means to me”, ACS New Haven Local Section, March 31, 2019.
K.L. Lee, “The
Discovery of IRAK4 candidate PF-06650833” and “A career in medicinal
chemistry”, Northeastern University Student Affiliates of the American Chemical
Society, Boston, MA, February 28, 2019.
K.L. Lee,
“The discovery of an IRAK4 clinical candidate from fragment-based drug design”,
Harvard-Pfizer Symposium, Harvard University, Cambridge, MA, April 18, 2017.
K.L. Lee, “Lead generation strategies: Discovery of a potent, selective
and lipophilic efficient IRAK4 inhibitor, a clinical candidate from
fragment-based drug design”, Gordon Research Conference on Medicinal Chemistry,
Colby-Sawyer College, New London, NH, August 7-12, 2016.
K. Lee* C. Allais, C. Ambler, D. Anderson, B. Boscoe, A. Bree, J.
Brodfuehrer, M. Bunnage, C. Choi, S. Chung, K. Curran, J. Day, C.
Dehnhardt, A. Dermenci, S. Drozda, R. Frisbie, L. Gavrin, J. Goldberg, S. Han,
M. Hegen, D. Hepworth, B. Jacobson, I. Kilty, S. Kortum, A. Lee, F. Lovering,
M. Lowe, J. Mathias, E. Murphy, N. Papaioannou, A. Patny, B. Pierce, S. Ramsey,
V. Rao, E. Saiah, J. Shin, H. Soutter, J. Strohbach, P. Symanowicz, J.
Thomason, J. Trzupek, R. Vargas, F. Vincent, X. Wang, A. Winkler, S. Wright, J.
Yan, C. Zapf, “Discovery of clinical candidate PF-0-6650833: A potent,
selective, and efficient inhibitor of IRAK4 from fragment-based drug design”,
251st ACS Meeting and Exposition, San Diego, CA, Mar. 13-17,
2016.
K. Lee*, R. Naven, F. Shah, N. Greene, C. Northcott, M. Dowty, T. Smeal,
S. Yamazaki, D. Hepworth, “Delivering safety and efficacy in kinase
inhibitors”, 250th ACS Meeting and Exposition, Boston, MA, Aug.
16-20, 2015.
K.L. Lee*, Y. Hu, J. Condon, N. Green, S. Guler, L. Jennings, D. Joseph-McCarthy,
D. Wilson, L. Xing, A. Bree, D. Goodwin, E. Li, S. Mohan, S. Shakya, M. Shen,
V. Spaulding, Q. Wang, Z. Xu, C. Nickerson-Nutter, “Cyanoquinoline inhibitors
of Lck, a Src family kinase”, poster, Gordon Research Conference on Natural
Products, Tilton, NH, July 22-27, 2012.
K.L. Lee*, R. Vargas, L. Chen, H.-G. Lombart, W. Wang, M. Behnke, J.
Nunez, S. Tam, N. Mollova, X. Xu, M.W.H. Shen, E. Murphy, M. Ramarao, C.L.
Nickerson-Nutter, J.D. Clark and J.C. McKew, “Pyrimidines: A new core for cPLA2a inhibitors”,
poster, Gordon Research Conference on Natural Products, Tilton, New Hampshire,
July 26-31, 2009.
K.L. Lee*, L. Chen, R. Vargas, P. Thakker, S. Tam, N. Mollova, X. Xu,
M.W.H. Shen, M. Hegen, C.L. Nickerson-Nutter, C. Williams, S.J. Goldman, S.
Marusic, J. Pelker, M. Hassan-Zahraee, V. Clerin, T.M. Smith, B. Tchernychev,
G. Vlasuk, M. Collins, J.D. Clark and J.C. McKew, “The discovery of cPLA2a inhibitors with
efficacy in animal models of arthritis, asthma, multiple sclerosis, thrombosis
and atherosclerosis”, poster, Gordon Research Conference on Medicinal
Chemistry, New London, New Hampshire, Aug. 5-10, 2007.
K.L. Lee*, M. L. Behnke, L. Chen, M.A. Foley, J. Nunez, R. Vargas, W.
Wang, S. Tam, M. Shen, N. Mollova, X. Xu, Louis Leung, D.G. Goodwin, C.
Nickerson-Nutter, C. Williams, J.D. Clark and J.C. McKew, “Indole phenyl
sulfonamide cPLA2a inhibitors for the treatment of inflammation”, oral presentation,
231st ACS National Meeting, Atlanta, GA, Mar. 26-30, 2006.
K. Lee*, R. Vargas, H.-G. Lombart and J. McKew, “Palladium-catalyzed
reactions with microwave heating: Examples from the cPLA2a inhibitor program
at Wyeth Research”, invited speaker, Symposium on Microwave Synthesis and Other
New Drug Discovery Technologies organized by Biotage, Boston, MA, May 26, 2005.
K.L. Lee*, J.C. McKew, M. Behnke, L. Chen, M. Foley, Y. Hu, P. M. Thakker,
J. Thomason, L. C. Wooder, K. Wu, F.-W. Sum and S. Tam, “Discovery of a new
class of anti-inflammatory: Indole cPLA2a inhibitors”, oral
presentation, 227th ACS National Meeting, Anaheim, CA, Mar.
28-Apr. 1, 2004.