Genentech Internal
ZHONGHUA PEI, PH.D.
GENENTECH, INC.
650-467-1542
pei.zhonghua@gene.com
Highlights of Professional Experience and Achievements
Senior Scientist, Discovery Chemistry Department, Genentech, Inc (2009.6 -present)
Scientist, Discovery Chemistry, Genentech, Inc (2007.6-2009.6)
A Cancer Immunotherapy project (2013.9- 2014.2 then 2014.12 to present) Chemistry team
leader
Led the chemistry team: led the team (total of ~ 18 FTE across Genentech, Argenta & Wuxi) to
pick 4 series as the lead to optimize.
ADC (Antibody-Drug Conjugate) Project (2014.3-2014-12)
Designed and synthesized linker drugs to improve therapeutic index of ADCs.
ITK project (2010. 2 – 2013.12) Project team leader
Led a multi-disciplinary project team of ~ 25 FTEs (biology, chemistry, DMPK, safety etc) at
multiple sites (internal and two external CROs) to discover small molecule ITK (a protein kinase )
inhibitors for anti-inflammatory indication. Primary responsibilities include setting strategies and
goals for the project, securing enough resources for the project and giving updates at RRC
reviews and project reviews, coordinating efforts from different functional groups and external
CROs, contribute scientifically in my own discipline by designing target molecules and influence
the design of the team.
Team identified the most potent and selective ITK inhibitors known in the literature. Team solved
multiple challenges: potency, solubility and cytotoxicity. The optimized compounds demonstrated
robust in vivo modulation yet did not demonstrate efficacy in the OVA asthma model despite good
target coverage.
mTRO Project (2007.7- 2009. 12) Chemistry team leader
Led the mTOR (a lipid kinase) chemistry team (~ 11 internal chemists and 2-3 CRO chemists).
Major responsibilities include designing and implementing medicinal chemistry strategies,
chairing chemistry team meeting, contributing to setting project goals, coordinating with other
functional groups such as early group, computer-aided design, pharmacology, DMPK to ensure
efficient compound design, synthesis, selection and profiling, overseeing chemists’ work at CRO,
providing updates at project meeting and reviews.
Discovered the lead series by scaffold hopping. Led the chemistry to successfully transition from ESR
to LSR and quickly to the discovery of Genentech drug candidate GDC-0349, which was approved for
early development (ED-ready and ED-go). ED team successfully filed IND and FPI occurred in May
2011. Member of the GDC-0349 ED team (12 months).
Notable Organizational Responsibilities
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Led a small team (~ 5 chemists) to work with Cheminformatic group to evaluate new Electronic
Laboratory Notebook (ELN). 2008
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Led Educational Short Course Committee of Discovery Chemistry Department to select topics
and courses for the department. Implemented three courses (usually 1-2 day).
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Examined and participated in due-diligence of 5 in-license opportunities of therapeutic
programs/molecules/technologies.
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Led a small team (~ 5 chemists) to work with cheminformatic group to develop G-number
report tool, which facilitates the summary and presentation of project data (2012).
Abbott Laboratories, Abbott Park, IL, 1997.7-2007.2
Research Investigator (2004.1 - 2007.2)
Assoc. Research Investigator (2001.3 - 2003.12)
Senior Research Chemist /Research Chemist (1997.7-2001.3)
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Key outcome includes: (1) primary inventor of Abbott drug development candidate (DDC) ABT-341, a
potent, selective, safe and efficacious DPP4 inhibitor for treatment of type 2 diabetes: designed &
synthesized the candidate molecule, designed the scaffold and improved the potency by 110-fold; (2) CoInventor of Abbott first-generation drug development candidate (ABT-279) of DPP4, which entered into
human clinical trials; was first to identify the C5 of pyrrolidine to modify for IP and potency improvement;
(3) team contributor of the LFA/ICAM-1antagonists drug candidate (IC747, licensed to ICOS/Biogen) went
to phase II clinical trial for inflammatory disease.
 Made major contributions to four other drug discovery programs: (a) protein tyrosine phsophatase 1B
(PTP1B) inhibitors for diabetes: designed the synthetic route that allowed quick SAR and was widely
adapted by the team; (b) DPP4-NEP dual inhibitor, (c) vitamin D receptor (VDR) agonists for treatment of
renal diseases: designed most of the targets (>80%) of the project; and (d) diacylglycerol Oacylotransferase type 1 (DGAT-1) inhibitor.
 New Target Committee member of Metabolic Disease (2005-02006): provided drugability assessment to
proposed targets.
Education
Massachusetts Institute of Technology, Cambridge, MA. Ph.D in Organic chemistry under Prof. Satoru
Massamune.
 Thesis: Studies Toward the Stereoselective Total Synthesis of Tedanolide
 ARCO scholarship (1997-98).
Rensselaer Polytechnic Institute, Troy, NY. M. Sc. organic/polymer chemistry
 Thesis under Prof. James A. Moore entitled “Structure-Property Relationship in Poly(enaminonitriles).”
University of Science and Technology of China Hefei, China. B. Sc. Department of Applied
Chemistry/Material Science and Technology.
 Honors: People’s Scholarship (four consecutive years).
Professional Training & Development
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Molecular Recognition Workshop. 1-day short course on principals of molecular interactions and
structure-based design. Presented to Genentech Chemistry Department by Prof. François
Diederich. October, 2011.
Chemical Aspects of Metabolism-Related Toxicity. 1-day short course on bioactivation and
strategies of minimizing toxicities of small molecules drugs. Presented to Genentech Chemistry
Department by Prof. Thomas Baillie. August, 2011.
Heterocyclic Chemistry, A Drug-Oriented Approach. 2-day short course on synthesizing
heterocycles useful in medicinal chemistry. Presented to Genentech by William H. Pearson. April
2011.
Situational Self-Leadership. Half-day short-course presented to managers by Genentech & Ken
Blanchard Companies. October, 2010.
Catalytic Cross-Coupling Reactions. 2-day short course presented to Genentech by Prof. Victor
Snieckus, April 2010
Scientific leadership course offered to gRED managers by Ed O’Reilly. 4 sessions, each 1.5
hours, 2010.
Immunology short course. Presented to Genentech Discovery Chemistry Department by Monica
Ranes-Goldberg.2010
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Cancer Biology Basics.1-day short course. Presented to Genentech Discovery Chemistry
Department by Monica Ranes-Goldberg, 2009
Designing Drugs with Optimal in vivo Activity after Oral Adminstration. 1-day short course on
optimizing metabolism and oral absorption. Presented to Abbott by Profs. Ronald T. Borchardt,
Kim Brouwer and Dhiren Takker, September 2004.
Technical Writing. Abbott, 2000.
Professional Affiliations & Community Service
American Chemical Society (ACS, Since 1994)
American Association of Cancer Research (AACR)
Chinese American Biopharmaceutical Association (CABS): ~ 3,000 members and participants
 President (2013-14); oversee CABS strategy and operation
 President-elect (2012-13): organized 2013 BioPacific Conference, which attracted by ~
600 attendees;
 Executive Committee member, four terms (2009-2014)
Publications in Refereed Journals (34), reviews and book chapters (6)
40. Sun, Y.; Zhou, M.; Lesch, J.; Senger, K.; Francis, R.;Barrett, K.; Burch, J.; Webster, J.
D.; Chen, Y.; Eastham-Anderson, J.; Ngu, H.; Li, O.; Staton, T.;Jackman, J.; Wu, L.;
Ghilardi, N.; Alaoui Ismaili, M. H.; Lee1, Pei, Z.; W. P.; DeVoss, J.; Zarrin, A.
A. ITK kinase inhibition reduces Fas ligand expression and activation induced cell death
to induce T cell hyperplasia after repeated antigenic challenge. Manuscript submitted to
Nature Medicine.
39. Burch, Jason D.; Barrett, Kathy; Chen, Yuan; DeVoss, Jason; Eigenbrot, Charles;
Goldsmith, Richard; Ismaili, M. Hicham A.; Lau, Kevin; Lin, Zhonghua; Ortwine, Daniel
FZarrin, A. A.; McEwan, P. A; Barker, J. F.; Ellebrandt, C.; Kordt, D.; Stein, D. B.;
Wang X.; Chen, C.; Hu, B.; Xu, X.; Yuen, P-W.; Pei, Z.* J. Med. Chem. 2015, 58, 38063816 .
38. Trani, G; Barker, J J.; Bromidge, S M.; Brookfield, F. A.; Burch, J. D.; Chen, Y.;
Eigenbrot, C.; Heifetz, A.; Ismaili, M. Hicham A.; Johnson, A.; Krulle, T. M.;
MacKinnon, C. H.; Maghames, R.; McEwan, P. A.; Montalbetti, C. A. G. N.; Ortwine, D.
F.; Perez-Fuertes, Y.; Vaidya, D. G.; Wang, X; Zarrin, A. A.; Pei, Z. Bioorg. Med. Chem.
Lett. 2014, 24, 5818-5823.
37. Burch, J. D.; Lau, K.; Barker, J. J.; Brookfield, F.; Chen, Y.; Chen, Y.; Eigenbrot, C.;
Ellebrandt, C.; Ismaili, M. H. A.; Johnson, A.; Kordt, D.; MacKinnon, C. H.; McEwan, P.
A.; Ortwine, D. F.; Stein, D. B.; Wang, X.; Winkler, D.; Yuen, P.-W.; Zhang, Y.; Zarrin,
A. A.; Pei, Z. J. Med. Chem. 2014, 57, 5714-5727.
36. Pastor, R. M.; Burch, J. D.; Magnuson, S.; Ortwine, D. F.; Chen, Y.; De La Torre, K.;
Ding, X.; Eigenbrot, C.; Johnson, A.; Liimatta, M.; Liu, Y.; Shia, S.; Wang, X.; Wu, L.;
Pei, Z. Discovery and optimization of Indazoles as potent and selective interleukin-2
inducible T cell kinase (ITK) inhibitors. Bioorg. Med. Chem. Lett. 2014, 24, 24482452.
35. MacKinnon, C. H.; Lau, K.; Burch, J. D.; Chen, Y.; Dines, J.; Ding, X.; Eigenbrot, C. E.;
Heifetz, A.; Jaochico, A.; Johnson, A.; Kraemer J.; Kruger, S.; Krulle, T. M.; Liimatta,
M.; Ly, J.; Maghames, R.; Montalbetti, C. A. G. N.; Ortwine, D. F.; Perez-Fuertes, Y.;
Shia, S.; Stein, D. B.; Trani, G.; Vaidya, D. G.; Wang, X.; Bromidge, S. M.; Wu, L. C.;
Pei, Z.* Structure-based design and synthesis of potent benzothiazole inhibitors of
Interleukin-2 inducible T cell kinase (Itk). Bioorg. Med. Chem. Lett. 2013, 23, 63316335.
34. Lee, W.; Ortwine, D. F.; Bergeron, P.; Lau, K.; Lin L.; Malek, S.; Nonomiya, J.; Pei, Z.;
Robarge, K. D.; Schmidt, S.; Sideris, S.; Lyssikatos, J. P. A Rapid Hit to Lead Discovery
of Novel N-Methylated Imidazolo-, Pyrrolo- and Pyrrazolo-Pyrimidines as Potent and
Selective mTOR Inhibitors. Bioorg. Med. Chem. Lett. 2013, 23, 5097-5104.
33. Estrada, A. A., Shore, D. G., Blackwood, E., Chen, Y-H., Deshmukh, G., Ding, X.,
DiPasquale, A. G., Epler, J. A., Friedman, L. S., Koehler, M. F. T., Liu, L., Malek. S.,
Nonomiya, J., Ortwine, D. F., Pei, Z., Siders, S., St-Jean, F., Trinh, L., Truong, T.,
Lyssikatos, J. P. Pyrimidoaminotropanes as Potent, Selective and Efficacious Small
Molecule Kinase Inhibitors of the Mammalian Target of Rapamycin (mTOR). J. Med.
Chem. 2013, 56, 3090-3101.
32. Pei, Z*., Blackwood, E.; Liu, L.; Malek, S.; Belvin, M.; Koehler, M. F. T.; Ortwine, D.
F.; Chen, H.; Cohen, F.; Kenny, J. R.; Bergeron, P.; Lau, K.; Ly, C.; Zhao, X.; Estrada,
A.; Truong, T.; Epler, J. A.; Nonomiya, J.; Trinh, L.; Sideris, S.; Lesnick, J.; m Bao, L.;
Vijapurkar, U.; Mukadam, S.; Tay, G.; Deshmukh, G.; Chen, Y-H.; Ding, X.; Friedman,
L. S.; Lyssikatos, J. P. Discovery and Biological Profiling of Potent and Selective mTOR
Inhibitor GDC-0349. ACS Med. Chem. Lett, 2013, 4, 103-107.
31. Koehler, M.F. T.; Bergeron, P.; Blackwood, E.; Bowman, K. K.;Chen, Y-H.; Deshukh,
G.; Ding, X.; Epler, J.; Estrada, A. A.; Lau, K.; Lee, L.; Liu, L.; Ly, C.; Malek, S.;
Nonomiya, J.; Oeh, J.; Ortwine, D. F.; Sampath, D.; Sideris, S.; Trinh, L.; Reuong, T.;
Wu, J.; Pei, Z.; Lyssikatos, J. P. Potent, Selective and Orally Bioavailable Inhibitors of
Mammalian Target of Rapamycin (mTOR) Kinase Syntergistically Combine with PI3K
Inhibitors to Produce Tumor Regression In Vivo. J. Med. Chem. 2012, 55, 10958-10971.
30. Vijapurkar, K,; Robillard, L.; Zhou, S.; Deqtyarev, M.; Lin, K.; Troung, T.; Tremayne, J.;
Ross, L. B.; Pei, Z.; Friedman, L. S.; Blackwood, E. M.; Belvin, M. mTOR Kinase
Inhibition Potentiates Apoptosis of PI3K and MEK Inhibitors in diagnostically Defined
Subpopulations. Cancer Lett. 2012, 326, 168-175.
29. Pei, Z. Marketed Dipeptidyl Peptidase IV (DPP4) Inhibitors. In New Therapeutic
Approaches for Type 2 Diabetes: Small Molecule Approaches. Ed. Robert M Jones, RSC
Publishing, 2012. ISBN 978-1-84973-414-1
28. Cohen, F., Bergeron, P.; Blackwood, E.; Bowman, K. K.; Chen, H.; DiPasquale, A. G.;
Epler, J. A.; Epler, J. A.; Koehler, M. F. T.; Lau, K.; Liwis, C.; Liu, L.; Ly, C. Q.; Malek,
S.; Nonomiya, J.; Ortwine, D. F.; Pei, Z.; Robage, K. D.; Sideris, S.; Trinh, L.; Truong,
T.; Wu, J.; Zhao, X.; Lyssikatos, J. P. Potent, Selective, and Orally Bioavailable
Inhibitors of Mammalian Target of Rapamycin (mTOR) Kinase Based on a Quaternary
Substituted Dihydrofuropyrimidine. J. Med. Chem. 2011, 54, 3426-3435.
27. Pei, Z. From the bench to the bedside: Dipeptidyl Peptidase IV Inhibitors, a New Class of
Oral Antihyperglycemic Agents. Curr, Opin. Drug Discov. & Develop. 2008, 11, 512532. Cited at least 39 times.
26. Pei, Z.*; Li, X.; von Geldern, T. W.; Longenecker, K.; Pireh, D.; Stewart, K. D.; Backes,
B. J.; Lai, C.; Lubben, T. H.; Ballaron, S. J.; Beno, D. W. A.; Kempf-Grote, A. J.; Sham,
H. L. and Trevillyan, J. M. Discovery and Structure-and-Activitivy Relationship of
Piperidine- and Piperdinone-constrained Phenethylamines as Novel, Potent and selective
Dipeptidyl Peptidase IV Inhibitors. J. Med. Chem. 2007, 50, 1983-1987.
Cited at least 48 times.
25. Backes, B. J.; Longenecker, K.; Hamilton, G. L.; Stewart, K.; Lai, C.; Kopecka, H.; von
Geldern, T. W.; Madar, D. J.; Pei, Z.; Lubben, T. H.; Zinker, B. A.; Tian, Z.; Ballaron, S.
J.; Stashko, M. A.; Mika, A. K.; Beno, D. W. A.; Kempf-Grote, A. J.; Black-Schaefer, C.;
Sham, H. L.; Trevillyan, J. M.. Pyrrolidine-Constrained Phenethylamines: The Design of
Potent, Selective and Pharmacologically Efficacious Dipeptidyl Peptidase IV (DPP4)
Inhibitors from a lead-like screening hit. Bioorg. Med. Chem. Lett. 2007, 17, 2005-2012.
24. Pei, Z*; Li, X.; von Geldern, T. W.; Madar, D. J.; Longenecker, K.;Yong, H.; Lubben, T.
H.; Stewart, K. D.; Zinker, B. A.; Backes, B. J.; Judd, A. S.; Mulhern, M.; Ballaron, S. J.;
Stashko, M. A.; Mika, A. K.; Beno, D. W. A.; Reinhart, G. A.; Fryer, R. M.; Preusser, L.
C.; Kempf-Grote, A. J.; Sham H. L.; and Trevillyan, J. M. Discovery of ((4R,5S)-5Amino-4-(2,4,5- trifluorophenyl)-cyclohex-1-enyl)-(3- (trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methanone (ABT-341), a Highly Potent, Selective,
Orally Efficacious, and Safe Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type
2 Diabetes. J. Med. Chem. 2006, 49, 6439-6442.
23. Madar, D. J.; Kopecka, H.; Pireh, D.; Yong, H.; Pei, Z.; Li, X.; Wiedeman, P.; Djuric, S.
W.; von Geldern, T. W.; Fickes, M.; Bhagavatula, L.; McDermott, T.; Wittenberger, S.;
Richards, S. J.; Longenecker, K.; Stewart, K.; Lubben, T. H.; Ballaron, S. J.; Stashko, M.
A.; Long, M.; Wells, H.; Zinker, B. A.; Mika, A. K.; Beno, D. W. A. Kempf-Grote, A. J.;
Polakowski, J.; Segreti, J.; Reinhart, G. A.; Fryer, R.; Sham, H. L. and Trevilliyan, J. M.
Discovery of 2-[4-{{2-(2S, 5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279); a very potent, selective,
effective and well tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment
of diabetes. J. Med. Chem. 2006, 49, 6416-6420.
22. Longenecker, K. L.; Stewart, K. D.; Madar, D. J.; Jakob, C. G.; Fry, E. H.; Wilk, S.; Lin,
C. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T. H.; Yong, H.; Pireh, D.; Pei, Z.;
Basha, F.; Wiedeman, P. E.; von Geldern, T. W.; Trevillyan, J. M.; Stoll, V. S. Crystal
Structures of DPP-IV (CD26) from Rat Kidney Exhibit Flexible Accommodation of
Peptidase-Selective Inhibitors. Biochem. 2006, 45, 7474-7482.
21. Pei, Z*.; Li, X.; Longenecker, K.; von Geldern, T. W.; Wiedeman, P. E.; Lubben, T. H.;
Zinker, B. A.; Stewart, K.; Ballaron, S. J.; Stashko, M. A.; Mika, A. K.; Beno, D. W. A.;
Long, M.; Wells, H.; Kempf-Grote, A. J.; Madar, D. J.; McDermott, T. S.; Bhagavatula,
L.; Fickes, M. G.; Pireh, D.; Solomon, L. R.; Lake, M. R.; Edalji, R.; Fry, E. H.; Sham,
H. L.; Trevillyan, J. M. Discovery, Structure-Activity Relationship, and Pharmacological
Evaluation of (5-Substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as Potent
Dipeptidyl Peptidase IV Inhibitors. J. Med. Chem. 2006, 49, 3520-3535. Featured on
Health & Medicine Week. Cited at least 39 times.
20. Pei, Z.*; Liu, G.; Lubben, T.H.; Szczepankiewicz, B. G. Inhibition of Protein Tyrosine
Phosphatase 1B for the Treatment of Diabetes and Obesity. Frontiers in Medicinal
Chemistry Volume 3, 335-368, Betham Sci. Pub. Ltd. 2006. Cited at least 57 times.
19. Pei, Z*.; Liu, G.; Lubben, T.H.; Szczepankiewicz, B. G. Inhibition of Protein Tyrosine
Phosphatase 1B as a Potential Treatment of Diabetes and Obesity. Current
Pharmaceutical Design. 2004, 10, 3481-3504.
18. Zhao, H.; Liu, G.; Xin, Z.; Serby, M.D; Pei, Z.; Szczepankiewicz, B.G; Hajduk, P.J.;
Abad-Zapatero, C.; Hutchins, C.W.; Lubben, T.H.; Ballaron, S.J.; Haasch, D.L;
Kaszubska, W.; Rondinone, C. M.; Trevillyan, J.M.; Jirousek, M. R. Isoxazole carboxylic
acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors. Bioorg. Med. Chem. Lett.
2004, 14, 5543-5546. Cited at least 50 times.
17. Xin, Z.; Liu, G.; Abad-Zapatero, C.; Pei, Z.; Szczepankiewicz, B.G.; Li,X.;
Zhang, T.; Cha.Hutchins, C. W.; Hajduk, P. J.; Ballaron, S. J.; Stashko, M. A.;
Lubben, T. H.; Trevillyan, J. M. and Jirousek, M. R. Identification of a
Monoacid-Based, Cell Permeable, Selective Inhibitor of Protein Tyrosine
Phosphatase 1B. Bioorg. Med. Chem. Lett. 2003, 13, 3947-3950. Cited at least 45 times.
16. Pei, Z*; Li, X.; Liu, G.; Abad-Zapatero, C.; Lubben, T.; Zhang, T.; Ballaron, S. J.;
Hutchins, C. W.; Trevillyan, J. M.; Jirousek, M. R. Discovery and SAR of Novel, Potent
and Selective Protein Tyrosine Phosphatase 1B Inhibitors. Bioorg. Med. Chem. Lett.
2003, 13, 3129-3132. Cited at least 21 times.
15. Liu, G.; Xin, Z.; Pei, Z.; Hajduk, P. J.; Abad-Zapatero, C.; Hutchins, C. W.; Zhao, H.;
Lubben, T. H.; Ballaron, S. J.; Haasch, D. L.; Kaszubska, W.; Rondinone, C. M.;
Trevillyan, J. M.; Jirousek, M. R. Fragment Screening and Assembly: A Highly Efficient
Approach to a Selective and Cell Active Protein Tyrosine Phosphatase 1B Inhibitor. J.
Med. Chem. 2003, 46, 4232-4235.
One of the pioneering research papers on fragment-based drug discovery. Cited at least
122 times.
14. Liu, G.; Xin, Z.; Liang, H.; Abad-Zapatero, C.; Hadjuk, P. J.; Janowick, D.;
Szczepankiewicz, B. G.; Pei, Z.; Hutchins, C. W.; Ballaron, S. J.; Stashko, M. A.;
Lubben, T. H.; Berg, C. E.; Rodinone, C. M.; Trevillyan, J. M.; Jirousek, M. R. Selective
Protein Tyrosine Phosphatase 1B Inhibitors: Targeting the Second Phosphotyrosine
Binding Site with Non-Carboxylic Acid-Containing Ligands. J. Med. Chem. 2003, 46,
3437-3440. Cited at least 84 times
13. Xin, Z.; Oost, T. K.; Abad-Zapatero, C.; Hajduk, P. J.; Pei, Z.; Szczepankiewicz, B. G.;
Hutchins, C. W.; Ballaron, S. J.; Stashko, M. A.; Lubben, T.; Jirousek, M. R.; Liu, G.
Potent, selective inhibitors of protein tyrosine phosphatase 1B. Bioorg. Med. Chem. Lett.
2003, 13, 1887-1890.
12. Liu, G.; Szczepankiewicz, B. G.; Pei, Z.; Janowick, D.A.; Xin, Z.; Hajduk, P. J.; AbadZapatero, C. ;Liang, H.; Hutchins, C. W.; Fesik, S. W.; Ballaron, S. J.; Stashko, M. A.;
Lubben, T.; Mika, A. K.; Zinker, B. A.; Trevillyan, J. M.; Jirousek, M. R. Discovery and
Structure –Activity Relationship of Oxalylarylaminobenzooic Acids as Inhibitors of
Protein Tyrosine Phoshoatase 1B. J. Med. Chem. 2003, 46, 2093-2103.
Cited at least 52 times.
11. Szczepankiewicz, B. G.; Liu, G.; Hajduk, P. J.; Abad-Zapatero, C.; Pei, Z.; Xin, Z.;
Lubben, T. H.; Trevillyan, J. M.; Stashko, M. A.; Ballaron, S. J.; Liang, H.; Huang, F.;
Hutchins, C. W.; Fesik, S. W.; Jirousek, M. R. Discovery of a Potent, Selective Protein
Tyrosine Phosphatase 1B Inhibitor Using a Linked-Fragment Strategy. J. Am. Chem. Soc.
2003; 125, 4087-4096. Cited at least 163 times.
10. Kurukulasuriya, R.; Link, J. T.; Madar, D. J.; Pei, Z.; Rohde, J. J.; Richards , S. J.;
Souers, A. J.;.Szczepankiewicz, B. G. Potential Drug Targets and Progress Towards
Pharmacological Inhibition of Hepatic Glucose Inhibition. Curr. Med. Chem. 2003, 10,
123-153
9. Kurukulasuriya, R.; Link, J. T.; Madar, D. J.; Pei, Z.; Rohde, J. J.; Richards , S. J.;
Souers, A. J.;.Szczepankiewicz, B. G. Prospects for Pharmacologic Inhibition of Hepatic
Glucose Production Curr. Med. Chem. 2003, 10, 99-12
8. Winn, M.; Reilly, E. B.; Liu, G.; Huth, J. R.; Jae, H-S.; Freeman, J,; Pei, Z.; Xin, Z.;
Lynch, J.; Kester, J.; von Geldern, T. W.; Leitza, S.; DeVries, P.; Dickinson, R.;
Mussatto, D.; Okasinski, G. F. Discovery of Novel p-Arylthio Cinnamides as Antagonists
of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1
Interaction. 4. Structure-Activity Relationship of Substituents on the Benzene Ring of the
Cinnamide. J. Med. Chem. 2001, 44, 4393-4403. Cited at least 52 times.
7. Pei, Z.*, Xin, Z.; Liu, G.; Li, Y.; Reilly, E. B.; Lubbers, N.; Huth, J. R.; Link, J. T.; von
Geldern, T. W.; Cox, B. F.; Leitza, S.; Gao, Y.; Marsh, K. C.; Devries, P; Okasinski, G.
F. Discovery of Novel p-Arythio Cinnamides as Antagonists of Leukocyte FunctionAssociated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 3. Amide (C-Ring)
Structure-Activity Relationship and Improvement of Overall Properties of Arylthio
Cinnamides. J. Med. Chem. 2001, 44, 2913-2920. Cited at least 29 times.
6. Link, J. T.; Sorensen, B.; Liu, G.; Pei, Z.; Reilly, E. B.; Leitza, S.; Okasinski, G.
Discovery and SAR of Diarysulfide Cyclopropylamide LFA-1/ICAM-1 Interaction
Antagonists. Bioorg. Med. Chem. Lett. 2001, 11, 973-976.
5. Liu, G.; Link, J. T.; Pei, Z.; Reilly, E. B.; Leitza, S.; Nguyen, B.; Marsh, K. C.;
Okasinski, G. F.; von Geldern, T. W.; Ormes, M.; Fowler, K.; Gallatin, M. Discovery of
Novel p-Arythio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen1/Intracellular Adhesion Molecule-1 Interaction. 1. Identification of an Additional
Binding Pocket Based on an Anilino Diaryl Sulfide Lead. J. Med. Chem. 2000, 43, 40254040. Cited at least 117 times.
4. Xin, Z.; Pei, Z.; von Geldern, T. W.; Jirousek, M. A Practical and Efficient
Intramolecular Michael Addition of Ureas to -unsaturated Esters. Tetrahedron Lett.
2000, 41, 1147-1150.
3. Liu, J-F.; Abiko, A.; Pei, Z.; Buske, D. C.; Masamune, S. Attainment of Syn-Selectivity
for Boron-Mediated Asymmetric Aldol Reactions of Carboxylic Esters. Tetrahedron Lett.
1998, 39, 1873-1876. Cited at least 57 times.
2. Xu, W.; Cui, J.; Wang, Y.; Pei, Z.; The Synthesis and Characterization of Ba-crosslinked
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Patents
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R.; Hengeveld, John E.; Li, Xiaofeng; McLaughlin, Maureen A.; Noonan, William T.;
Pei, Zhonghua; Wu-Wong, Jinshyun Ruth. Vitamin D receptor activators and methods
of making. US 2009131379 A1. Published May 21, 2009; (b) Von Geldern, Thomas
W.; Burkalow, Jufang H.; Barnes, David M.; Haight, Anghony R.; Hengeveld, John E.;
Li, Xiaofeng; McLaughlin, Maureen A.; Noonan, William T.; Pei, Zhonghua; Wu-Wong,
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24. Souers, Andrew J.; Gao, Ju; Hansen, Todd Matthew; Iyengar, Rajesh R.; Kym, Philip R.;
Liu, Bo X.; Pei, Zhonghua; Yeh, Vince; Zhao, Gang. Preparation of heterocyclic
inhibitors of diacylglycerol O-acylotransferase type 1 (DGAT-1) enzyme. WO
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23. Pei, Z; von Geldern, T. W.; Madar, D. J.; Li, X.; Basha, F.; Yong, H.; Longenecker, K.;
Backes, B. J.; Judd, A. J.; Mulhern, M. M.; Stewart, K. D. Cyclohexenylamine
derivatives and as inhibitors of dipeptidyl peptidase-iv (DPP-IV) and their preparation,
pharmaceutical compositions and use in the treatment of various diseases US 2007
0049596. Provisional filling Aug. 30, 2005; Published 2007-3-1.
22. Backes, Bradley J.; Hamilton, Gregory L.; Kopecka, Hana A.; Lai, Chunqiu;
Longenecker, Kenton L.; Madar, David J.; Pei, Zhonghua; Stewart, Kent D.; Von
Geldern, Thomas W. Preparation of pyrrolidin-3-amines as inhibitors of dipeptidyl
peptidase IV for use against type II diabetes and other diseases. U.S. Pat. Appl. Publ.
(2006), 30pp. US 2006264433 A1 Published November 23, 2006.
21. (a) Akritopoulou-Zanze, Irini; Darczak, Daria; Dinges, Jurgen; Djuric, Stevan W.; Hoff,
Ethan D.; Kopecka, Hana A.; Patel, Jyoti R.; Pei, Zhonghua; Shuai, Qi; Sarris, Kathy;
Sham, Hing L.; Wiedeman, Paul E. Preparation and pharmaceutical compositions of
pyrrolidine derivatives as inhibitors of dipeptidyl peptidase-iv (DPP-iv). US
2005215603 A1 Published September 29, 2005;
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Ethan D.; Kopecka, Hana A.; Patel, Jyoti R.; Pei, Zhonghua; Shuai, Qi; Sarris, Kathy;
Sham, Hing L.; Wiedeman, Paul E. Preparation and pharmaceutical compositions of
pyrrolidine derivatives as inhibitors of dipeptidyl peptidase-iv (DPP-iv). US
2005209249 A1 Published September 22, 2005.
19. (a) Pei, Zhonghua; Li, Xiaofeng; Longenecker, Kenton L.; Sham, Hing L.; Wiedeman,
Paul E. A preparation of L-prolylpyrrolidinecarbonitrile, useful as inhibitors of
dipeptidyl peptidase-IV. US 2005131019 A1 Published June 16, 2005, Priority: US
2003-500079 20030904; (b)Pei, Zhonghua; Li, Xiaofeng; Longenecker, Kenton L.;
Sham, Hing L.; Wiedeman, Paul E. Preparation of pyrrolidine-2-carbonitrile derivatives
and their use as inhibitors of dipeptidyl peptidase-IV (DPP-IV). PCT Int. Appl. (2005),
182 pp. CODEN: PIXXD2 WO 2005023762 A1 20050317Pei, Z.; Li, X.;
Longenecker, K.; Sham, H.; Wiedeman, Pyrrolidine-2-carbonitrile Derivatives and their
Use as Inhibitors of Dipeptidyl Deptidase-IV (DPP-IV). WO 2005/023762 A1. Priority:
US 2003-655428 20030904 (Sept. 4, 2003).
18. (a) Madar, David J.; Djuric, Stevan W.; Michmerhuizen, Melissa J.; Kopecka, Hana A.;
Li, Xiaofeng; Longenecker, Kenton L.; Pei, Zhonghua; Pireh, Daisy; Sham, Hing L.;
Stewart, Kent D.; Szczepankiewicz, Bruce G.; Wiedeman, Paul E.; Yong, Hong.
Preparation of cyanopyrrolidine derivatives and pharmaceutical compositions thereof as
inhibitors of dipeptidyl peptidase-iv (dpp-iv). US 2005215784 A1 Published
September 29, 2005; (b) Madar, D.; Pei, Z.; Pireh, D.; Djuric, S. W.; Wiedeman, P. E.;
Yong, H; Feenstra, M. J.; Kopecka, H; Li, X; Longenecker, K.; Sham, H. L.; Stewart, K.
D.; Szczepankiewicz, B. G. Pharmaceutical Compositions as Inhibitors of Dipeptidyl
Peptidase-IV (DPP-IV). WO2004026822. Priority Date: Sept. 19, 2002.
17. Madar, David J.; Djuric, Stevan W.; Michmerhuizen, Melissa J.; Kopecka, Hana A.;
Li, Xiaofeng; Longenecker, Kenton L.; Pei, Zhonghua; Pireh, Daisy; Sham, Hing L.;
Stewart, Kent D.; et al Preparation of N-aminoacyl pyrrolidine-2-carbonitriles and
related compounds as inhibitors of dipeptidyl peptidase-IV (DPP-IV) useful against
type II diabetes and other disorders US 20040259843 A1. Published 2004-12-23.
16. Link, James; Liu, Gang; Pei, Zhonghua; Von Geldern, Tom; Winn, Martin; Xin, Zhili;
Boyd, Steven A.; Zhu, Gui-Dong; Freeman, Jennifer C.; Gunawardana, Indrani W.;
Staeger, Michael A.; Jae, Hwan-Soo; Lynch, John K.; Wang, Sheldon. Preparation of 2or 4-(phenylthio)cinnamides as cell adhesion-inhibiting antiinflammatory and immunesuppressive compounds. US 6878700 B1 Published April 12, 2005. Priority: US 98114097 19981229; US 99-474517.
15. Liu, G.; Szczepankiewicz, B. G.; Pei, Z.; Xin, Z.; Janowick, David A. Selective protein
tyrosine phosphatatase inhibitors. US 6,972,340 B2. Published Dec 6, 2005. Filed on Aug
29, 2001.
14. Xin, Zhili; Liu, Gang; Pei, Zhonghua; Szczepankiewicz, Bruce G.; Serby, Michael D.;
Zhao, Hongyu. Preparation of arylisoxazolecarboxylates as protein - tyrosine
phosphatase ( PTP1B ) inhibitors. US 2004214870 A1 Published October 28, 2004.
13. Xin, Zhili; Liu, Gang; Pei, Zhonghua; Szczepankiewicz, Bruce G.; Serby, Michael D.;
Zhao, Hongyu. Preparation of arylazole derivatives as protein-tyrosine phosphatase
inhibitors. US 2004167188 A1 Published August 26, 2004. Application: US 2003366830 20030214. Priority: CAN 141:225493 AN 2004:701813
12. Liu, Gang; Xin, Zhili; Pei, Zhonghua; Li, Xiaofeng; Szczepankiewicz, Bruce G.;
Janowick, David A.; Oost, Thorsten K. Preparation of amino(oxo)acetic acid derivatives
as selective protein tyrosine phosphatase inhibitors. US 2002169157 A1 Published
November 14, 2002. Priority: US 2000-650922 20000829; US 2000-228651
20000829; US 2001-918928 20010731; US 2001-941471 20010829.
11. Liu, Gang; Pei, Zhonghua. Preparation of dichlorophenoxy(benzyl)acetic acid
derivatives as protein tyrosine phosphatase inhibitors. US 2002077347 A1
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10. Liu, Gang; Szczepankiewicz, Bruce G.; Pei, Zhonghua; Xin, Zhili; Janowick, David A.
Preparation of amino(oxo)acetic acids as selective protein tyrosine phosphatase
inhibitors. U.S. Pat. Appl. Publ. (2002), 44 pp., US 2002072516 A1. Published June
13, 2002.
9. Liu, Gang; Szczepankiewicz, Bruce G.; Pei, Zhonghua; Xin, Zhili; Oost, Thorsten K.;
Janowick, David A. Preparation of amino(oxo)acetic acids as protein tyrosine
phosphatase inhibitors. WO 0218323 A2 Published March 07, 2002. Application: WO
2001-US26906 20010829. Priority: US 2000-650922 20000829; US 2000-228651
20000829; US 2001-918928 20010731.
7. Liu, G.; Li, Y.; Janowick, D.; Pei, Z. Amino(oxo) acetic acid protein tyrosine
phosphatase inhibitors. US 6,627,767 B2. Date of patent: Sept. 30, 2003.
8. Liu, G. Pei, Z. Protein Tyrosine Phosphatase Inhibitors. US 6472545, Issued: Oct. 29,
2002. (WO 0218363 A2 20020307).
7. (a) Liu, G.; Szczepankiewicz, Pei, Z.; Xin, Z.; Oost, T. K.; Janowick, D. A. Preparation
of amino(oxo)acetic Acids as Protein Tyrosine Phosphatase inhibitors. WO 02 018323.
Application: WO 2001-US26906 20010829. Priority: US 2000-650922 20000829; US
2000-228651 20000829; US 2001-918928 20010731. (b) Liu, Gang; Li, Yihong;
Janowick, David A.; Pei, Zhonghua. Preparation of amino(oxo)acetic acid protein
tyrosine phosphatase inhibitors. WO 2002018321 A2. Published March 07, 2002.
5. Liu, G.; Li, Y.; Janowick, D. A.; Pei, Z. Amino(oxo) acetic acid protein tyrosine
phosphatase inhibitors. US 20020035136 (WO 0218321).
4. Link, James; Liu, Gang; Pei, ZhongHua; von Geldern, Tom; Winn, Martin; Xin, Zhili;
Boyd, Steven A.; Zhu, Gui-Dong; Freeman, Jennifer C.; Gunawardana, Indrani W.;
Staeger, Michael A.; Jae, Hwan-Soo; Lynch, John K.; Wang, Sheldon. Cell adhesioninhibiting antiinflammatory and immune-suppressive compounds. US 6,878,700.
Published April 12, 2005.
3. Link, James; Liu, Gang; Pei, Zhonghua; Von Geldern, Thomas W.; Winn, Martin; Xin,
Zhili; Wang, Sheldon; Boyd, Steven A.; Zhu, Gui-Dong; Freeman, Jennifer C.;
Gunawardana, Indrani W.; Staeger, Michael A.; Jae, Hwan-soo; Lynch, John K.
Preparation of 2- or 4-(phenylthio)cinnamides as cell adhesion-inhibiting
antiinflammatory and immune-suppressive compounds. PCT Int. Appl. (2000), 476
pp. WO 0059880 A1 Published October 12, 2000.
2. Link, J.; Liu, G.; Pei, Z.; Von Geldern T. W; Winn, M.; Xin, Z.; Wang, S.; Boyd, S. A;
Zhu, G-D.; Freeman, J.R C; Gunawardana I. W; Staeger M. A. Cell Adhesion-inhibiting
Antiinflammatory and Immune-suppressive Compounds. WO 0059880 Published Oct.
12, 2000.
1. Link, J.; Liu, G.; Pei, Z.; Von Geldern T. W; Winn, M.; Xin, Z. Cell adhesion-inhibiting
anti-inflammatory and immune-suppressive compounds. US 6,110,922. Published August
29, 2000. Filed: December 29, 1998.
Presentations and Abstracts
14. Zhonghua Pei. Structure-based design of potent ITK inhibitors. Invited oral presentation
at FloHet-2014 Florida Heterocyclic and Synthetic Conference. March 3, 2014,
Gainsville, FL.
13. Zhonghua Pei. Discovery and Profiling of Potent and Selective mTOR Inhibitor GDC0349. Oral presentation at European Federation of Medicinal Chemistry (EFMC)International Symposium of Medicinal Chemistry (ISMC), Berlin, Germany, September
2012.
12. Zhonghua Pei. Rational Design of Potent, Selective, Efficacious and Safe DPP4
Inhibitors as a Treatment of Type 2 Diabetes. Invited oral presentation for case study at
Molecular Medicine Tri-Conference: Mastering Medicinal Chemistry, February 28March 2, 2007, San Francisco, CA
11. Zhonghua Pei. Discovery of ABT-341, a Potent, Selective and Potentially Nextgeneration DPP4 Inhibitor for Treatment of Diabetes. Invited oral Presentation at
MedChem Europe, February 20-21, 2007, Barcelona, Spain.
10. Pei, Z; Li, X.; von Geldern, T. W.; Madar, D. J.; Longenecker, K.;Yong, H.; Zinker, B.
A.; Lubben, T. H.; Stewart, K. D.; Backes, B. J.; Stashko, M. A.; Ballaron, S. J.; Beno,
D. W. A.; Mika, A. K.; Reinhart, G. A.; Fryer, R. M.; Preusser, L. C.; Kempf-Grote, A.
J.; Sham H. L.; and Trevillyan, J. M. Discovery of cyclohexene-constrained
phenethylamine, ABT-341: A highly potent, selective, safe and orally available
dipeptidyl peptidase IV inhibitor for the treatment of Type 2 diabetes. Oral presentation,
Abstract # MEDI 4 at The 232nd ACS National Meeting, San Francisco, CA, September
10-14, 2006
9. Li, X.; Pei, Z; von Geldern, T. W.; Madar, D. J.; Longenecker, K.;Yong, H.; Lubben, T.
H.; Stewart, K. D.; Ballaron, S. J.; Stashko, M. A.; Mika, A. K.; Beno, D. W. A.;
Reinhart, G. A.; Kempf-Grote, A. J.; Sham H. L.; and Trevillyan, J. M. Synthesis and the
structure-activity relationships of cyclohexene-constrained phyenethylamine as
Dipeptidyl Peptidase IV inhibitor. Poster, Abstract # MEDI 417 at The 232nd ACS
National Meeting, San Francisco, CA, September 10-14, 2006.
8. Shuai, Qi; Patel, Jyoti; Zanze, Irini; Dinges, Jurgen; Wiedeman, Paul E.; Pei, Zhonghua;
Michmerhuizen, Melissa; Hoff, Ethan; Kalvin, Douglas; Von Geldern, Thomas; Lubben,
Tom; Ballaron, Steven; Stashko, Mike; Zinker, Brad; Djuric, Stevan W.; Beno, David;
Kempf-Grote, Anita; Mika, Amanda; Farb, Tomas; Perham, Matthew; Adler, Andrew;
Trevillyan, James; Sham, Hing L. Acyl thiazolidides-novel potent DPP-IV inhibitors.
Poster. Abstracts of Papers, 230th ACS National Meeting, Washington, DC, United
States, Aug. 28-Sept. 1, 2005 (2005), MEDI-303.
8. Madar, D.; Pireh, D.; Pei, Z.; Yong, H.; Kopecka, H.; Wiedeman; P.; Li, X.; Djuric, S.;
Longenecker, K.; Stewart, K.; Ballaron, S.; Stashko, M.; Lubben, T.; Sham, H.;
Trevillyan J.; Dipeptidyl Peptidase (DPP)-IV Inhibitors: A Potential New Treatment for
Type II Diabetes. Gordon Conference on Natural Products, Tilton, N.H., 2004.
6. Chen, Yixian; Richards, Steven; Shuai, Qi; Patel, Jyoti; Madar, David; Yong, Hong; Pei,
Zhonghua; von Geldern, Thomas W.; Longenecker, Kenton L.; Stewart, Kent; Lubben,
Tom; Ballaron, Steven; Stashko, Mike; Trevillyan, James; Sham, Hing. Discovery of
potent DPP-IV inhibitors. Poster. Abstracts of Papers, 230th ACS National Meeting,
Washington, DC, United States, Aug. 28-Sept. 1, 2005 (2005), MEDI-301.
5. Liu, G.; Abad-Zapatero, C.; Szczpankiewicz, B.; Hajduk, P.; Pei, Z.; Xin, Z.; Janowick,
D.; Liang, L.; Hutchins, C.; Ballaron, S.; Stashko, M.; Lubben, T.; Trevillyan, J.;
Jirousek, M. Discovery of Competitive, Potent, and Selective Protein Tyrosine
Phosphatase 1B Inhibitors. American Chemical Society 222nd National Meeting, Orlando,
FL April 7-11, 2002, Abstract # MEDI 02.
4. PEI, Z.; ZINKER, B. A.; GUM, R. J.; JACOBSON, P. B.; BALLARON, S. J.;
TREVILLYAN, J. M.; NGUYEN, B.; MARSH, K. C.; LIU, G.; XIE, N. Y.;
JIROUSEK, M. R. (2R)-2-(2’,6’-Dichloro-4’-dibenzo(b,d)furan-4’’-ylphenoxy)-3phenylpropanoic Acid (A-321842) as a Protein Tyrosine Phosphatase 1B (PTP-1B)
Inhibitor with Anti-Diabetic Effects in ob/ob Mice. Poster. American Diabetes
Association, 61st Scientific Sessions, Philadelphia, PA, June 22-26, 2001. Abstract #
1524-P.
3. Szczepankiewicz, B. G.; Liu, G.; Tasker, A, S.; Sorensen, B. K.; von Geldern, T. W.;
Jae, H-S.; Winn, M.; Gwaltney II, S. L.; Kester, J.A.;. Pei, Z.; Wu-Wong, J.R.; Gehrke,
L.; Chiou, W.J.; Credo, R.B.; Lee, J.Y.; Warner, R.B.; Alder, J.D.; Nukkala, M.A.;
Zielinski, N.A.; Marsh, K.C.; Rosenberg , S.H. Antimitotic agents with activity in
multidrug-resistant tumor cell lines. American Chemical Society 221st National Meeting,
San Diego, CA, April 1-5, 2001, Abstract # MEDI 139.
2. Pei, Z.; Xin, Z.; Liu, G.; Li, Y.; Winn, M.; Link, J.T.; vonGeldern, T.; Reily, E.; Leitza,
S.; DeVries, P.; Gao, Y.; Okasinski, G.F. Potent antagonists of leukocyte functionassociated antigen-1/intracellular adhesion molecule-1 interaction. Poster. American
Chemical Society 221st National Meeting, San Diego, CA, April 1-5, 2001, Abstract #
MEDI 246.
1. Liu, G.; Link, J.T.; Pei, Z.; von Geldern, T.W.; Reilly, E.B.; Leitza, S.; Nguyen, B.;
Marsh, K.C.; Okasinski, G.F. Discovery of novel p-arylthio cinnamides as antagonists of
LFA-1/ICAM-1 interaction. I. Identification of an additional binding site based on an
anilino diaryl sulfide lead. American Chemical Society 220th National Meeting,
Washington DC, August 20-24, 2000, Abstract # MEDI 171.