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15 results on '"Pakulska, Urszula"'

1. P986: COMBINATION JAK1/2 AND CDK8/19 INHIBITION DEMONSTRATES ENHANCED EFFICACY IN MYELOPROLIFERATIVE NEOPLASMS

Author

Zaroogian, Zachary, primary, Adamczyk, Elżbieta, additional, Moszyńska, Adrianna, additional, Obacz, Marta, additional, Pakulska, Urszula, additional, Durham, Benjamin, additional, Mazan, Milena, additional, Mowla, Shoron, additional, Wnęk, Katarzyna, additional, Somasundara, Amritha Varshini Hanasoge, additional, Barczuk, Beata, additional, Gołas, Aniela, additional, Levine, Ross, additional, Rzymski, Tomasz, additional, and Rampal, Raajit K, additional

Published
2023
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2. Multiomics Analysis Confirms Effective Target Engagement for RVU120 - a First-in-Class CDK8/19 Kinase Inhibitor in AML and MR-MDS Patients and Reveals the Mechanism of Action

Author

Rzymski, Tomasz, primary, Sroka-Porada, Agnieszka, additional, Kozakowska, Magdalena, additional, Głowniak-Kwitek, Urszula, additional, Bukowska-Strakova, Karolina, additional, Obacz, Marta, additional, Littlewood, Peter, additional, Kuś, Kamil, additional, Goller, Kristina, additional, Kęska, Kinga, additional, Pakulska, Urszula, additional, Kozłowska-Tomczyk, Kamila, additional, Madej, Monika, additional, Mazan, Milena, additional, Juszczynski, Przemyslaw, additional, Zaucha, Jan M., additional, Zarzycka, Agnieszka, additional, Angelosanto, Noemi, additional, Nogai, Hendrik, additional, and Brzózka, Krzysztof, additional

Published
2022
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3. Abstract 2647: RVU120, a selective CDK8/CDK19 inhibitor, demonstrates efficacy against hormone-independent breast cancer cells in vitro and in vivo

Author

Pakulska, Urszula, primary, Obacz, Marta, additional, Gołas, Aniela, additional, Mazan, Milena, additional, Masiejczyk, Magdalena, additional, Stachowicz, Agata, additional, Martyka, Justyna, additional, Combik, Michał, additional, Kęska, Kinga, additional, Wiklik, Katarzyna, additional, Goller, Kristina, additional, Adamczyk, Elżbieta, additional, Brzózka, Krzysztof, additional, and Rzymski, Tomasz, additional

Published
2022
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4. Abstract P5-17-13: Selective CDK8/CDK19 inhibitor RVU120 demonstrates efficacy against hormone-independent breast cancer cells in vitro and in vivo

Author

Rzymski, Tomasz, primary, Gołas, Aniela, additional, Mazan, Milena, additional, Pakulska, Urszula, additional, Masiejczyk, Magdalena, additional, Stachowicz, Agata, additional, Martyka, Justyna, additional, Combik, Michał, additional, Wiklik, Katarzyna, additional, Goller, Kristina, additional, Obacz, Marta, additional, Adamczyk, Elżbieta, additional, and Brzózka, Krzysztof, additional

Published
2022
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5. Discovery of Cycloalkyl[c]thiophenes as Novel Scaffolds for Hypoxia-Inducible Factor-2α Inhibitors

Author

Buchstaller, Hans-Peter, Sala-Hojman, Ada, Leiendecker, Matthias, Albers, Joachim, Anlauf, Uwe, Berges, Nina, Dong, Liming, Fuchß, Thomas, Germann, Martina, Knehans, Tim, Krier, Mireille, Lecomte, Marc, Müller, Daniel, Müller, Sandra R., Leuthner, Birgitta, Lindemann, Ralph, Musil, Djordje, Nowak, Mateusz, Reither, Vivian, Rettig, Corinna, Schindler, Christina E. M., Pakulska, Urszula, Spuck, Dieter, Wegener, Ansgar, and Zarębski, Adrian

Abstract

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors induced in diverse pathophysiological settings. Inhibition of HIF-2α has become a strategy for cancer treatment since the discovery that small molecules, upon binding into a small cavity of the HIF-2α PAS B domain, can alter its conformation and disturb the activity of the HIF dimer complex. Herein, the design, synthesis, and systematic SAR exploration of cycloalkyl[c]thiophenes as novel HIF-2α inhibitors are described, providing the first chemotype featuring an alkoxy–aryl scaffold. X-ray data confirmed the ability of these inhibitors to induce perturbation of key amino acids by appropriately presenting key pharmacophoric elements in the hydrophobic cavity. Selected compounds showed inhibition of VEGF-A secretion in cancer cells and prevention of Arg1 expression and activity in IL4-stimulated macrophages. Moreover, in vivo target gene modulation was demonstrated with compound 35r. Thus, the disclosed HIF-2α inhibitors represent valuable tools for investigating selective HIF-2α inhibition and its effect on tumor biology.

Published
2023
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6. RVU120 (SEL120) CDK8/19 Inhibitor - a Drug Candidate for the Treatment of MDS Can Induce Erythroid Differentiation

Author

Pakulska, Urszula, primary, Obacz, Marta, additional, Goller, Kristina, additional, Combik, Michal, additional, Keska, Kinga, additional, Zaucha, Jan, additional, Zarzycka, Ewa, additional, Mazan, Milena, additional, Mikula, Michal, additional, Cybulska, Magdalena, additional, Polak, Anna, additional, Juszczynski, Przemyslaw, additional, Flygare, Johan, additional, Chen, Jun, additional, Brzozka, Krzysztof, additional, Järås, Marcus, additional, Dziedzic, Katarzyna, additional, Angelosanto, Noemi, additional, Shamsili, Setareh, additional, and Rzymski, Tomasz, additional

Published
2021
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7. Preclinical and Clinical Signs of Efficacy of RVU120 (SEL120), a Specific CDK8/19 Inhibitor in DNMT3A-Mutated AML

Author

Rzymski, Tomasz, primary, Pakulska, Urszula, additional, Abboud, Camille, additional, Burris, Howard A., additional, Solomon, Scott R., additional, Obacz, Marta, additional, Goller, Kristina, additional, Combik, Michal, additional, Zaucha, Jan, additional, Mazan, Milena, additional, Mikula, Michal, additional, Cybulska, Magdalena, additional, Polak, Anna, additional, Juszczynski, Przemyslaw, additional, Järås, Marcus, additional, Chapellier, Marion, additional, Flygare, Johan, additional, Zawadzka, Magdalena, additional, Strakova, Karolina Bukowska, additional, Brzozka, Krzysztof, additional, Shamsili, Setareh, additional, and Angelosanto, Noemi, additional

Published
2021
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8. Abstract 1018: SEL120, a CDK8/CDK19 inhibitor, possesses strong multilineage differentiation potential in AML

Author

Pakulska, Urszula, primary, Adamczyk, Elzbieta, additional, Dziedzic, Katarzyna, additional, Wiklik, Katarzyna, additional, Combik, Michal, additional, Mikula, Michal, additional, Golas, Aniela, additional, Obacz, Marta, additional, Masiejczyk, Magdalena, additional, Juszczynski, Przemyslaw, additional, Cybulska, Magdalena, additional, Mazan, Milena, additional, Brzozka, Krzysztof, additional, and Rzymski, Tomasz, additional

Published
2021
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10. Targeting CDK8/CDK19 to Disrupt Leukemic Stem Cell-like Population in Acute Myeloid Leukemia: Exploring RVU120 As a Promising Frontline Therapy

Author

Mazan, Milena, Pakulska, Urszula, Moszyńska, Adrianna, Sroka-Porada, Agnieszka, Szade, Krzysztof Tomasz, Mikula, Michał, Kozakowska, Magdalena, Juszczyński, Przemysław, Wiklik, Katarzyna, Göller, Kristina, Obacz, Marta, Abboud, Camille N., Zaucha, Jan Maciej, Marańda, Ewa Lech, Angelosanto, Noemi, Nogai, Hendrik, and Rzymski, Tomasz

Published
2023
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11. Novel Clinically Useful Inhibitor of Mediator Complex, RVU120, Relives Differentiation Block in MDS/AML

Author

Ajibade, Opeyemi, Pakulska, Urszula, Rabinovich, Emma, Fromowitz, Ariel, Sahu, Srabani, Aminov, Sarah, Ramachandra, Nandini, Aluri, Srinivas, Gordon Mitchell, Shanisha, Carbajal, Milagros, Keska-Izworska, Kinga, Combik, Michał, Obacz, Marta, Adamczyk, Elżbieta, Zaucha, Jan M., Zarzycka, Ewa, Juszczynski, Przemyslaw, Boultwood, Jacqueline, Pellagatti, Andrea, Pradhan, Kith, Steidl, Ulrich, Shastri, Aditi, Zhao, Rongbao, Mazan, Milena, Rzymski, Tomasz, and Verma, Amit

Published
2023
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15. Discovery of Cycloalkyl[ c ]thiophenes as Novel Scaffolds for Hypoxia-Inducible Factor-2α Inhibitors.

Author

Buchstaller HP, Sala-Hojman A, Leiendecker M, Albers J, Anlauf U, Berges N, Dong L, Fuchß T, Germann M, Knehans T, Krier M, Lecomte M, Müller D, Müller SR, Leuthner B, Lindemann R, Musil D, Nowak M, Reither V, Rettig C, Schindler CEM, Pakulska U, Spuck D, Wegener A, and Zarębski A

Subjects
Humans, Transcription Factors, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit, Basic Helix-Loop-Helix Transcription Factors metabolism, Thiophenes pharmacology
Abstract

Hypoxia-inducible factors (HIFs) are heterodimeric transcription factors induced in diverse pathophysiological settings. Inhibition of HIF-2α has become a strategy for cancer treatment since the discovery that small molecules, upon binding into a small cavity of the HIF-2α PAS B domain, can alter its conformation and disturb the activity of the HIF dimer complex. Herein, the design, synthesis, and systematic SAR exploration of cycloalkyl[ c ]thiophenes as novel HIF-2α inhibitors are described, providing the first chemotype featuring an alkoxy-aryl scaffold. X-ray data confirmed the ability of these inhibitors to induce perturbation of key amino acids by appropriately presenting key pharmacophoric elements in the hydrophobic cavity. Selected compounds showed inhibition of VEGF-A secretion in cancer cells and prevention of Arg1 expression and activity in IL4-stimulated macrophages. Moreover, in vivo target gene modulation was demonstrated with compound 35r . Thus, the disclosed HIF-2α inhibitors represent valuable tools for investigating selective HIF-2α inhibition and its effect on tumor biology.

Published
2023
Full Text
View/download PDF

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