Joerg Weiske

Abstract 6978: Discovery and characterization of BAY-805, a potent and selective DUB inhibitor of ubiquitin specific peptidase USP21

Norbert Schmees, Fabian Göricke, U. Scheib, Raphael Boehm et autres

Abstract Deubiquitinases (DUBs) have recently become of high interest as some members of this protein class show potential for therapeutic interventions. The family of nearly 100 members is divided into 6 sub families. Their action is the cleavage of ubiquitin modifications from …

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Discovery of YAP1/TAZ pathway inhibitors through phenotypic screening with potent anti-tumor activity via blockade of Rho-GTPase signaling

Keith Graham, Philip Lienau, Benjamin Bader, Stefan Prechtl et autres

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Novel YAP1/TAZ pathway inhibitors identified through phenotypic screening with potent anti-tumor activity via blockade of GGTase-I / Rho-GTPase signaling

Keith Graham, Philip Lienau, Benjamin Bader, Stefan Prechtl et autres

SUMMARY This study describes the identification and target deconvolution of novel small molecule inhibitors of oncogenic YAP1/TAZ activity with potent anti-tumor activity in vivo. A high-throughput screen (HTS) of 3.8 million compounds was conducted using a cellular YAP1/TAZ reporter assay. Target deconvolution …

de, Afrique du Sud, nl, it, ch, dk (code pays fourni par la source)

T cell-mediated elimination of cancer cells by blocking CEACAM6–CEACAM1 interaction

J. Pinkert, Hans-Henning Boehm, Mark Trautwein, Wolf‐Dietrich Doecke et autres

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a cell surface receptor, is expressed on normal epithelial tissue and highly expressed in cancers of high unmet medical need, such as non-small cell lung, pancreatic, and colorectal cancer. CEACAM receptors undergo homo- and heterophilic …

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Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer

Sebastian M. Dieter, Christine Siegl, Paula Codó, Mario Huerta et autres

Novel treatment options for metastatic colorectal cancer (CRC) are urgently needed to improve patient outcome. Here, we screen a library of non-characterized small molecules against a heterogeneous collection of patient-derived CRC spheroids. By prioritizing compounds with inhibitory activity in a subset of-but …

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Discovery of the SMYD3 Inhibitor BAY-6035 Using Thermal Shift Assay (TSA)-Based High-Throughput Screening

Stefan Gradl, H. Steuber, Joerg Weiske, Magda Szewczyk et autres

SMYD3 (SET and MYND domain-containing protein 3) is a protein lysine methyltransferase that was initially described as an H3K4 methyltransferase involved in transcriptional regulation. SMYD3 has been reported to methylate and regulate several nonhistone proteins relevant to cancer, including mitogen-activated protein kinase …

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Identification of Small Molecules that Modulate Mutant p53 Condensation

Clara Lemos, Luise Schulze, Joerg Weiske, Hanna Meyer et autres

Structural mutants of p53 induce global p53 protein destabilization and misfolding, followed by p53 protein aggregation. First evidence indicates that p53 can be part of protein condensates and that p53 aggregation potentially transitions through a condensate-like state. We show condensate-like states of …

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Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction

Roman Christian Hillig, Brice Sautier, Jens Schroeder, Dieter Moosmayer et autres

Since the late 1980s, mutations in the RAS genes have been recognized as major oncogenes with a high occurrence rate in human cancers. Such mutations reduce the ability of the small GTPase RAS to hydrolyze GTP, keeping this molecular switch in a …

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Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

Duy Nguyen, Clara Lemos, Lars Wortmann, Knut Eis et autres

The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by …

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Abstract 689: Identification and optimization of novel chemical matter via a structure-based approach resulting in a probe for MTH1

Marcus Bauser, Anja Giese, Manuel Ellermann, Judith Guenther et autres

Abstract Cancer cells can form reactive oxygen species (ROS) due to altered redox regulation that affect desoxynucleosides triphosphates (dNTP) in particular. 8-oxo-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP) and 2-hydroxydeoxyadenosine-5'-triphosphate (2-OH-dATP) are the two most abundant oxidative nucleotide lesions in this respect. These undesired nucleoside triphosphates are …

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Abstract 1771: BAY 1834942 is an immunotherapeutic antibody blocking the novel immune checkpoint regulator CEACAM6 (CD66c)

Joerg Willuda, Mark Trautwein, J. Pinkert, Wolf‐Dietrich Doecke et autres

Abstract CEACAM6 (CD66c) was previously shown to act as a novel immune checkpoint regulator suppressing the activity of effector T cells against tumors (Witzens-Harig et al., Blood 2013). CEACAM6 is a GPI-linked protein that is strongly expressed at the tumor cell surface …

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Isoform-Selective ATAD2 Chemical Probe with Novel Chemical Structure and Unusual Mode of Action

Amaury E. Fernández‐Montalván, Markus Berger, Benno Kuropka, Seong Joo Koo et autres

ATAD2 (ANCCA) is an epigenetic regulator and transcriptional cofactor, whose overexpression has been linked to the progress of various cancer types. Here, we report a DNA-encoded library screen leading to the discovery of BAY-850, a potent and isoform selective inhibitor that specifically …

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