Natalia Ortiz Zacarías
Natalia Ortiz Zacarías is a Ph.D. student at the Division of Drug Discovery & Safety. She aims to gain new insight on the concepts of allosteric modulation and binding kinetics to improve the development of better drugs and the prediction of in-vivo outcomes.
My passion for Pharmaceutical Sciences started in my home-country, Mexico, where I did my bachelor studies on Biological and Pharmaceutical Chemistry. During my undergraduate studies I had the opportunity to gather experience in different disciplines of Pharmaceutical Sciences, by working as an intern in a community pharmacy, a drug information center and a hospital pharmacy. Later on, after my graduation, I worked for two years as a hospital pharmacist in a local hospital, where I focused on medication therapy management and pharmaceutical care.
Next to these professional experiences, I also assisted in a research project focused on biomaterials for controlled drug delivery, which inspired me to continue my studies in a research-oriented master program. This led me to perform my master studies in Leiden University, where I followed the MSc in Bio-Pharmaceutical Sciences from 2012-2014. Here I did two research internships and a literature review. First, I performed a 9-months internship at the department of Medicinal Chemistry, LACDR, where I worked on the characterization of the sodium binding pocket of the Adenosine A2A receptor. I performed my second 6-months internship at CHDR, where I worked on the simulation of multiple-dose regimen of fosfomycin as a potential therapy for multi-drug resistant infections.
These research experiences motivated me to continue with a PhD degree, and therefore, on November 2014 I started as a PhD student in the department of Medicinal Chemistry, under the supervision of Prof. IJzerman and Dr. Heitman. In these four years, I will focus on chemokines receptors, aiming to gain new insight on the concepts of allosteric modulation and binding kinetics to improve the development of better drugs and the prediction of in-vivo outcomes. For this, I will be using a combination of radioligand binding and functional assays.
- Patberg M., Isaak A., Füsser F., Ortiz Zacarías N.V., Vinnenberg L., Schulte J., Michetti L., Grey L., Horst C. van der, Hundehege P., Koch O., Heitman L.H., Budde T. & Junker A. (2021), Piperazine squaric acid diamides, a novel class of allosteric P2X7 receptor antagonists, European Journal of Medicinal Chemistry 226.
- Ortiz Zacarías N.V., Bemelmans M.P., Handel T.M., Visser K.E. de & Heitman L.H. (2021), Anticancer opportunities at every stage of chemokine function, Trends in Pharmacological Sciences 42(11): 912-928.
- Ortiz Zacarías N.V., Chahal K.K., Šimková T., Horst C. van der, Zheng Y., Inoue A., Theunissen E., Mallee L., Es D. van der, Louvel J., IJzerman A.P., Handel T.M., Kufareva I. & Heitman L.H. (2021), Design and characterization of an intracellular covalent ligand for CC chemokine receptor 2, Journal of Medicinal Chemistry 64(5): 2608-2621.
- Sommer F., Ortiz Zacarías N.V., Heitman L.H. & Meijer A.H. (2020), Inhibition of macrophage migration in zebrafish larvae demonstrates in vivo efficacy of human CCR2 inhibitors, Developmental and Comparative Immunology 116: 103932.
- Wagner S., Moura Gatti F., Silva D.G. de, Ortiz Zacarias N.V., Zweemer A.J.M., Hermann S., Maria M. de, Koch M., Weiss C., Schepmann D., Heitman L.H., Tschammer N., Kopka K. & Junker A. (2021), Development of the first potential nonpeptidic positron emission tomography tracer for the imaging of CCR2 receptors, ChemMedChem 16(4): 640-645.
- Ortiz Zacarías N.V., Veldhoven J.P.D. van, Hollander L.S. den, Dogan B., Openy J., Hsiao Y.Y., Lenselink E.B., Heitman L.H. & IJzerman A.P. (2019), Synthesis and Pharmacological Evaluation of Triazolopyrimidinone Derivatives as Noncompetitive, Intracellular Antagonists for CC Chemokine Receptors 2 and 5, Journal of Medicinal Chemistry 62(24): 11035-11053.
- Ortiz Zacarías N.V. (4 December 2019), The road to Insurmountability: Novel avenues to better target CC Chemokine Receptors (PhD thesis. Leiden Academic Centre for Drug Research (LACDR), Faculty of Science, Leiden University). Supervisor(s): IJzerman, A.; Heitman, L.
- Zacarias N.V.O., Veldhoven J.P.D. van, Portner L., Spronsen E. van, Ullo S, Veenhuizen M., Velden W.J.C. van der, Zweemer A.J.M., Kreekel R.M., Oenema K., Lenselink E.B., Heitman L.H.I & IJzerman A.P. (2018), Pyrrolone Derivatives as Intracellular Allosteric Modulators for Chemokine Receptors: Selective and Dual-Targeting Inhibitors of CC Chemokine Receptors 1 and 2, Journal of Medicinal Chemistry 61(20): 9146-9161.
- Ortiz Zacarías N.V., Lenselink E.B., IJzerman A.P., Handel T.M. & Heitman L.H. (2018), Intracellular Receptor Modulation: Novel Approach to Target GPCRs, Trends in Pharmacological Sciences 39(6): 547-559.
- Thum S., Kokornaczyk A.K., Seki T., De Maria M., Ortiz Zacarias N.V., Vries H. de, Weiss C., Koch M.l., Schepmann D., Kitamura M., Tschammer N., Heitman L.H., Junker A. & Wuensch B. (2017), Synthesis and biological evaluation of chemokine receptor ligands with 2-benzazepine scaffold, European Journal of Medicinal Chemistry 135: 401-413.
- Bot I., Ortiz Zacarias N.V., Witte W.E. de, Vries H. de, Santbrink P.J. van, Velden D. van der, Kroener M.J., Berg D.J. van den, Stamos D., Lange E.C.M. de, Kuiper J., IJzerman A.P. & Heitman L.H. (2017), A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy, Scientific Reports 2017(7): 52.
- Zheng Y., Qin L., Ortiz Zacarias N.V., Vries H. de, Han G.W., Gustavsson M., Dabros M., Zhao C., Cherney R.J., Carter P., Stamos D., Abagyan R., Cherezov V., Stevens R.C., IJzerman A.P., Heitman L.H., Tebben A., Kufareva I. & Handel T.M. (2016), Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists, Nature 540(7633): 458-461.
- Massink A., Gutiérrez-de-Terán H., Lenselink E.B., Ortiz Zacarías N.V., Xia L., Heitman L.H., Katritch V., Stevens R.C. & IJzerman A.P. (2015), Sodium Ion Binding Pocket Mutations and Adenosine A2A Receptor Function, Molecular Pharmacology 87(2): 305-13.
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