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Research ArticleDrug Discovery and Translational Medicine

Using Target Engagement Biomarkers to Predict Clinical Efficacy of MetAP2 Inhibitors

Pamela J. Farrell, Christopher J. Zopf, Huey-Jing Huang, Deepika Balakrishna, Corine Holub, James Bilakovics, Andrea Fanjul, Jennifer Matuszkiewicz, Artur Plonowski, Paul Rolzin, Urmi Banerjee, Jacques Ermolieff, Zacharia S. Cheruvallath, Christopher McBride, Darian Bartkowski, Crystal Mazur, Alok Pachori and Christopher J. Larson
Journal of Pharmacology and Experimental Therapeutics November 2019, 371 (2) 299-308; DOI: https://doi.org/10.1124/jpet.119.259028
Pamela J. Farrell
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Christopher J. Zopf
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Huey-Jing Huang
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Deepika Balakrishna
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Corine Holub
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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James Bilakovics
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Andrea Fanjul
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Jennifer Matuszkiewicz
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Artur Plonowski
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Paul Rolzin
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Urmi Banerjee
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Jacques Ermolieff
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Zacharia S. Cheruvallath
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Christopher McBride
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Darian Bartkowski
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Crystal Mazur
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Alok Pachori
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Christopher J. Larson
Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
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Article Information

vol. 371 no. 2 299-308
DOI 
https://doi.org/10.1124/jpet.119.259028
PubMed 
31537613

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0022-3565
Online ISSN 
1521-0103
History 
  • Received May 11, 2019
  • Accepted September 4, 2019
  • Published online October 11, 2019.

Article Versions

  • Earlier version (September 19, 2019 - 07:31).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics

Author Information

  1. Pamela J. Farrell,
  2. Christopher J. Zopf1,
  3. Huey-Jing Huang,
  4. Deepika Balakrishna,
  5. Corine Holub,
  6. James Bilakovics,
  7. Andrea Fanjul,
  8. Jennifer Matuszkiewicz,
  9. Artur Plonowski2,
  10. Paul Rolzin,
  11. Urmi Banerjee,
  12. Jacques Ermolieff,
  13. Zacharia S. Cheruvallath,
  14. Christopher McBride,
  15. Darian Bartkowski,
  16. Crystal Mazur,
  17. Alok Pachori, and
  18. Christopher J. Larson3
  1. Biological Sciences (P.J.F., H.-J.H., De.B., C.H., J.B., A.F., J.M., A.Pl., P.R., U.B., J.E., C.J.L.), Chemistry (Z.S.C., C.Mc.), and Drug Metabolism and Pharmacokinetics (Da.B.), Takeda California, San Diego, California; Modeling and Simulation, Takeda Boston, Cambridge, Massachusetts (C.J.Z.); and Translational Research Institute for Metabolism and Diabetes, Florida Hospital Campus, Orlando, Florida (C.Ma., A.Pa.)
  1. Address correspondence to:
    Dr. Pamela J. Farrell, Takeda California, 9625 Towne Center Drive, San Diego, CA 92121. E-mail: m.farrell{at}att.net
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Research ArticleDrug Discovery and Translational Medicine

MetAP2 Inhibitor Translational Pharmacology

Pamela J. Farrell, Christopher J. Zopf, Huey-Jing Huang, Deepika Balakrishna, Corine Holub, James Bilakovics, Andrea Fanjul, Jennifer Matuszkiewicz, Artur Plonowski, Paul Rolzin, Urmi Banerjee, Jacques Ermolieff, Zacharia S. Cheruvallath, Christopher McBride, Darian Bartkowski, Crystal Mazur, Alok Pachori and Christopher J. Larson
Journal of Pharmacology and Experimental Therapeutics November 1, 2019, 371 (2) 299-308; DOI: https://doi.org/10.1124/jpet.119.259028

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Research ArticleDrug Discovery and Translational Medicine

MetAP2 Inhibitor Translational Pharmacology

Pamela J. Farrell, Christopher J. Zopf, Huey-Jing Huang, Deepika Balakrishna, Corine Holub, James Bilakovics, Andrea Fanjul, Jennifer Matuszkiewicz, Artur Plonowski, Paul Rolzin, Urmi Banerjee, Jacques Ermolieff, Zacharia S. Cheruvallath, Christopher McBride, Darian Bartkowski, Crystal Mazur, Alok Pachori and Christopher J. Larson
Journal of Pharmacology and Experimental Therapeutics November 1, 2019, 371 (2) 299-308; DOI: https://doi.org/10.1124/jpet.119.259028
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