Dr. Wilbert de Witte joins esqLABS

Dr. Wilbert De Witte, a pharmacologist with a deep understanding of complex mechanisms, joined esqLABs on 1. August.



Dr. Wilbert de Witte joins esqLABS

Wilbert will conduct projects as a principal consultant and share his expertise in PBK-modeling of large molecules.

Wilbert is a Pharmacologist with a strong drive to understand complex mechanisms and the models that represent them.

Before joining esqLABS, he worked at Ablynx NV, later Sanofi Ghent, on the preclinical and clinical development of NANOBODY® therapeutics. He developed several PBPK and PBPK-QSP models as well as traditional TMDD and PKPD models for mechanistic analysis of in vitro, in vivo, and clinical data. He accumulated in-depth knowledge on the behavior of large molecules in different modalities and with various target binding characteristics.

Wilbert obtained his Master’s degree in Bio-Pharmaceutical Sciences from Leiden University (the Netherlands). For his PhD thesis, he studied the impact of drug-target binding kinetics on in vivo drug action. His PhD research was supervised by Prof. Liesbeth de Lange, Prof. Piet-Hein van der Graaf and Prof. Meindert Danhof at the department of Pharmacology at Leiden University.

List of peer-reviewed Publications

  1. Witte, W.E.A. de, Danhof, M., Graaf, P.H. van der, and Lange, E.C.M. de (2018). The implications of target saturation for the use of drug–target residence time Nat. Rev. Drug Disc. 18:82-84
  2. Witte, W.E.A. de, Versfelt, J.W., Kuzikov, M., Rolland, S., Georgi, V., Gribbon, P., Gul, S., Huntjens, D., Graaf, P.H. van der, Danhof, M., Fernandez-Montalvan, A., Witt, G., and Lange, E.C.M. de (2018). In vitro and in silico analysis of the effects of D2 receptor antagonist target binding kinetics on the cellular response to fluctuating dopamine concentrations. Br. J. Pharmacol. 175:4121-4136
  3. Vlot, A.H.C., Witte, W.E.A. de, Danhof, M., Graaf, P.H. van der, van Westen, G.J.P., and Lange, E.C.M. de (2018). Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling. AAPS J. 20:11
  4. Nederpelt, I., Kuzikov, M., Witte, W.E.A de, Schnider, P., Tuijt, B., Gul, S., IJzerman, A.P., Lange, E.C.M. de and Heitman, L.H. (2017). From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug- action. Sci. Rep. 7:14169
  5. Witte, W.E.A. de, Vauquelin, G., Graaf, P.H. van der, and Lange, E.C.M. de (2017). The influence of drug distribution and drug-target binding on target occupancy: The rate-limiting step approximation. Eur. J. Pharm. Sci. 109S:S83-S89
  6. Bot, I., Ortiz, N., de Witte, W., de Vries, H., van Santbrink, P.J., van der Velden, D., Kröner, M.J., van der Berg, D.J., Stamos, D., de Lange, E.C.M., et al. A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy. Sci. Rep. 2017, 7, 52
  7. Witte, W.E.A. de, Danhof, M., Graaf, P.H. van der, and Lange, E.C.M. de (2016). In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant. Trends Pharmacol. Sci. 37: 831–842.
  8. Witte, W.E.A. de, Wong, Y.C., Nederpelt, I., Heitman, L.H., Danhof, M., Graaf, P.H. van der, Gilissen, R.A.H.J and Lange, E.C.M. de (2015). Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients. Expert Opin. Drug Discov. 11: 45–63.
  9. Schuetz, D.A., Witte, W.E.A. de, Wong, Y.C., Knasmueller, B., Richter, L., Kokh, D.B., et al. (2017). Kinetics for Drug Discovery: an industry-driven effort to target drug residence time. Drug Discov. Today 22: 896–911.
  10. Dubois, V.F.S., Witte, W.E.A. De, Visser, S.A.G., Danhof, M., and Pasqua, O. Della (2016). Assessment of Interspecies Differences in Drug-Induced QTc Interval Prolongation in Cynomolgus Monkeys, Dogs and Humans. Pharm. Res. 33: 40–51.
  11. Delft, P. Van, Witte, W. De, Meeuwenoord, N.J., Heden Van Noort, G.J. Van Der, Versluis, F., Olsthoorn, R.C.L., et al. (2014). Design of a ribosyltriazole-annulated cyclooctyne for oligonucleotide labeling by strain-promoted alkyne-azide cycloaddition. European J. Org. Chem. 2014: 7566–7571

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