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Scientist Profile

Cornelis Hop

Director, Drug Metabolism & Pharmacokinetics
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"Many of us have relatives affected by debilitating and sometimes terminal diseases. It is hard to top the personal satisfaction that comes from knowing that we are improving and extending the lives of patients."
 

I joined Genentech in 2007 as director of the small molecule Drug Metabolism & Pharmacokinetics department. The mission of the DMPK department is to enable the discovery, selection, development, and commercialization of safe and effective medicines for significant unmet medical needs by elucidating the absorption, distribution, metabolism, elimination and pharmacokinetic properties of small molecule drug candidates. We accomplish this through application of state-of-the-art technologies and sciences of drug metabolism and disposition, bioanalysis, innovative thinking, effective collaboration and teamwork.

Drug discovery and development continues to be extremely challenging and success is only achievable by integrating the contributions from excellent scientists here at Genentech. Having everyone on one campus is ideal, because you can simply walk over and discuss the latest data and next steps.

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My Focus

Genentech's strength lies in its deep knowledge of the biology as it relates to oncology, immunology and, more recently, CNS disorders. Our goal is to contribute to small molecule drugs which will be as successful as Genentech's many biological drugs.

The ADME science related to small molecule drug discovery and development is a rapidly evolving field and we have great opportunities to apply the latest science to identify molecules that combine potency, efficacy, safety with superior drug metabolism and pharmacokinetic properties.

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Publications & Recognition
  • Determination of GDC-0449, a small-molecule inhibitor of the Hedgehog signaling pathway, in human plasma by solid phase extraction-liquid chromatographic-tandem mass spectrometry.
  • J Chromatogr B Analyt Technol Biomed Life Sci 2010 Mar 15; 878(9-10): 785-790.
  • Ding X, Chou B, Graham RA, Cheeti S, Percey S, Matassa LC, Reuschel SA, Meng M, Liu S, Voelker T, Lum BL, Rudewicz PJ, Hop CE.
  • View Abstract on PubMed
  • High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.
  • Curr Drug Metab 2008 Nov; 9(9): 847-53.
  • Hop CE, Cole MJ, Davidson RE, Duignan DB, Federico J, Janiszewski JS, Jenkins K, Krueger S, Lebowitz R, Liston TE, Mitchell W, Snyder M, Steyn SJ, Soglia JR, Taylor C, Troutman MD, Umland J, West M, Whalen KM, Zelesky V, Zhao SX.
  • View Abstract on PubMed
  • Use of nano-electrospray for metabolite identification and quantitative absorption, distribution, metabolism and excretion studies.
  • Curr Drug Metab 2006 Jun; 7(5): 557-63.
  • Hop CE.
  • View Abstract on PubMed
 
View All Publications & Recognition
 
  • University of Utrecht (The Netherlands) and University of Ottawa (Canada)
  • Chemistry, Ph.D.
  • 1988
  • University of Utrecht (The Netherlands)
  • Chemistry, M.Sc.
  • 1986
  • University of Utrecht (The Netherlands)
  • Chemistry, B.Sc.
  • 1984
Publications & Recognition
  • Determination of GDC-0449, a small-molecule inhibitor of the Hedgehog signaling pathway, in human plasma by solid phase extraction-liquid chromatographic-tandem mass spectrometry.
  • J Chromatogr B Analyt Technol Biomed Life Sci 2010 Mar 15; 878(9-10): 785-790.
  • Ding X, Chou B, Graham RA, Cheeti S, Percey S, Matassa LC, Reuschel SA, Meng M, Liu S, Voelker T, Lum BL, Rudewicz PJ, Hop CE.
  • View Abstract on PubMed
  • High throughput ADME screening: practical considerations, impact on the portfolio and enabler of in silico ADME models.
  • Curr Drug Metab 2008 Nov; 9(9): 847-53.
  • Hop CE, Cole MJ, Davidson RE, Duignan DB, Federico J, Janiszewski JS, Jenkins K, Krueger S, Lebowitz R, Liston TE, Mitchell W, Snyder M, Steyn SJ, Soglia JR, Taylor C, Troutman MD, Umland J, West M, Whalen KM, Zelesky V, Zhao SX.
  • View Abstract on PubMed
  • Use of nano-electrospray for metabolite identification and quantitative absorption, distribution, metabolism and excretion studies.
  • Curr Drug Metab 2006 Jun; 7(5): 557-63.
  • Hop CE.
  • View Abstract on PubMed
  • A semiquantitative method for the determination of reactive metabolite conjugate levels in vitro utilizing liquid chromatography-tandem mass spectrometry and novel quaternary ammonium glutathione analogues.
  • Chem Res Toxicol 2006 Mar; 19(3): 480-90.
  • Soglia JR, Contillo LG, Kalgutkar AS, Zhao S, Hop CE, Boyd JG, Cole MJ.
  • View Abstract on PubMed
  • p38 MAP kinase inhibitors: metabolically stabilized piperidine-substituted quinolinones and naphthyridinones.
  • Bioorg Med Chem Lett 2006 Jan 1; 16(1): 64-8.
  • Bao J, Hunt JA, Miao S, Rupprecht KM, Stelmach JE, Liu L, Ruzek RD, Sinclair PJ, Pivnichny JV, Hop CE, Kumar S, Zaller DM, Shoop WL, O'neill EA, O'keefe SJ, Thompson CM, Cubbon RM, Wang R, Zhang WX, Thompson JE, Doherty JB.
  • View Abstract on PubMed
  • Identification of a novel glutathione adduct of diclofenac, 4'-hydroxy-2'-glutathione-deschloro-diclofenac, upon incubation with human liver microsomes.
  • Drug Metab Dispos 2005 Apr; 33(4): 484-8.
  • Yu LJ, Chen Y, Deninno MP, O'Connell TN, Hop CE.
  • View Abstract on PubMed
  • In vitro metabolism of a new oxazolidinedione hypoglycemic agent utilizing liver microsomes and recombinant human cytochrome P450 enzymes.
  • J Pharm Biomed Anal 2005 Feb 23; 37(2): 351-8.
  • Agrawal AK, Hop CE, Pang J, Silva Elipe MV, Desai RC, Leung KH, Franklin RB.
  • View Abstract on PubMed
  • The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model.
  • Drug Metab Dispos 2005 Jan; 33(1): 165-74.
  • Doran A, Obach RS, Smith BJ, Hosea NA, Becker S, Callegari E, Chen C, Chen X, Choo E, Cianfrogna J, Cox LM, Gibbs JP, Gibbs MA, Hatch H, Hop CE, Kasman IN, Laperle J, Liu J, Liu X, Logman M, Maclin D, Nedza FM, Nelson F, Olson E, Rahematpura S, Raunig D, Rogers S, Schmidt K, Spracklin DK, Szewc M, Troutman M, Tseng E, Tu M, Van Deusen JW, Venkatakrishnan K, Walens G, Wang EQ, Wong D, Yasgar AS, Zhang C.
  • View Abstract on PubMed
  • In vitro metabolism of MK-0767 [(+/-)-5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[(4-trifluoromethyl)-phenyl] methyl]benzamide], a peroxisome proliferator-activated receptor alpha/gamma agonist. II. Identification of metabolites by liquid chromatography-tandem mass spectrometry.
  • Drug Metab Dispos 2004 Sep; 32(9): 1023-31.
  • Liu DQ, Karanam BV, Doss GA, Sidler RR, Vincent SH, Hop CE.
  • View Abstract on PubMed
  • The metabolic disposition of aprepitant, a substance P receptor antagonist, in rats and dogs.
  • Drug Metab Dispos 2004 Feb; 32(2): 246-58.
  • Huskey SE, Dean BJ, Doss GA, Wang Z, Hop CE, Anari R, Finke PE, Robichaud AJ, Zhang M, Wang B, Strauss JR, Cunningham PK, Feeney WP, Franklin RB, Baillie TA, Chiu SH.
  • View Abstract on PubMed
  • Identification of metabolites of a substance P (neurokinin 1 receptor) antagonist in rat hepatocytes and rat plasma.
  • Drug Metab Dispos 2002 Aug; 30(8): 937-43.
  • Hop CE, Wang Y, Kumar S, Elipe MV, Raab CE, Dean DC, Poon GK, Keohane CA, Strauss J, Chiu SH, Curtis N, Elliott J, Gerhard U, Locker K, Morrison D, Mortishire-Smith R, Thomas S, Watt AP, Evans DC.
  • View Abstract on PubMed
  • Importance of early assessment of bioactivation in drug discovery.
  • In: Doherty AM, editor. Annual reports in medicinal chemistry. Vol. 41. Amsterdam: Elsevier; 2006. p. 369-81.
  • CECA Hop, Kalgutkar AS, Soglia JR.
  • LC-MS in drug disposition and metabolism.
  • In: Caprioli RM, editor. Encyclopedia of mass spectrometry. Vol. 3, Pt. B. Amsterdam: Elsevier; 2006. p. 233-74.
  • Hop CECA.
  • Metabolite identification by LC-MS: Applications in drug discovery and development.
  • In: Chowdhury SK, editor. Identification and quantification of drugs, metabolites and metabolizing enzymes by LC-MS. Elsevier, Amsterdam: Elsevier; 2005. p. 123-58.
  • Hop CECA, Prakash C.
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Awards & Honors
  • Regional Award for Achievements in Mass Spectrometry
    ACS Mass Spectrometry Discussion Group, New Jersey Section
    2003
  • Professional Development Award
    University of Wisconsin - Madison
    1994
  • Royal Dutch Shell Travel Award
    1988
  • Special Recommendation of the Faculty of Science
    University of Utrecht
    1986

Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.