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概览

疾病领域	数量

感染	1
免疫系统疾病	1
肿瘤	1

排名前五的药物类型	数量

小分子化药	2

排名前五的靶点	数量

PAD4	1
STT3A x STT3B	1

关联

2

项与 Cellzome GmbH 相关的药物

STT3A/B Inhibitors(GSK)

靶点

STT3A x STT3B

作用机制

STT3A 抑制剂 [+1]

在研机构

Vir Biotechnology, Inc. [+2]

原研机构

GlaxoSmithKline LLC

在研适应症

病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

GSK484

靶点

PAD4

作用机制

PAD4抑制剂

在研机构

Cellzome GmbH

原研机构

Cellzome GmbH [+1]

在研适应症

自身免疫性疾病 [+2]

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期-

100 项与 Cellzome GmbH 相关的临床结果

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0 项与 Cellzome GmbH 相关的专利（医药）

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75

项与 Cellzome GmbH 相关的文献（医药）

2024-08-22·Journal of Medicinal Chemistry

Discovery of Potent STT3A/B Inhibitors and Assessment of Their Multipathogen Antiviral Potential and Safety

Article

作者: Pannirselvam, Malar ; Yim, Samantha ; Carabajal, Esteban ; Kowalski, Beatriz ; Peat, Andrew J. ; Lo, Gary ; Sweeney, David ; Zhou, Jiayi ; McAllaster, Michael ; Terrell, Ashley ; Mueller, Elizabeth A. ; Chen, Yi-Pei ; Jeyasingh, Sam ; Dalmas Wilk, Deidre ; Lehmann, Stephanie ; Momont, Corey ; Pearson, Neil ; Colas, Christophe ; Newby, Zachary ; Eberl, H. Christian ; Ranjan, Rohit ; Grosse, Johannes ; Cato, Matthew ; Gordon, Earl ; Fernandez, Beth ; Wang, Shuya ; Telenti, Amalio ; Hetzler, Belinda ; Safabakhsh, Pegah ; Cai, Haiying ; Cassidy, James ; Chen, Dingjun ; McHugh, Charles ; Plastridge, Bob ; Wang, Lisha ; Tse, Winston ; Bohan, Dana ; Soriaga, Leah ; Oladunni, Fatai ; Nigro, Maria ; Adolph, Ramona S. ; Talecki, Lindsey ; Bantscheff, Marcus ; Wedel, Laura ; Park, Arnold ; Darwech, Isra ; Bagchi, Parikshit ; Stokes, Neil ; Adams, Ashley M. ; Werner, Thilo ; Bartha, Istvan ; Chaudhary, Khuram W. ; Balce, Dale ; Hansen, Justin ; Pero, Joseph E. ; Barauskas, Ona ; Hwang, Seungmin ; Shapiro, Nathan D.

In the aftermath of the COVID-19 pandemic, opportunities to modulate biological pathways common to the lifecycles of viruses need to be carefully considered. N-linked glycosylation in humans is mediated exclusively by the oligosaccharyltransferase complex and is frequently hijacked by viruses to facilitate infection. As such, STT3A/B, the catalytic domain of the OST complex, became an intriguing drug target with broad-spectrum antiviral potential. However, due to the critical role N-linked glycosylation plays in a number of fundamental human processes, the toxicological ramifications of STT3A/B inhibition required attention commensurate to that given to antiviral efficacy. Herein, we describe how known STT3A/B inhibitor NGI-1 inspired the discovery of superior tool compounds which were evaluated in in vitro efficacy and translational safety (e.g., CNS, cardiovascular, liver) studies. The described learnings will appeal to those interested in the therapeutic utility of modulating N-linked glycosylation as well as the broader scientific community.

2024-03-22·Cancer Research

Abstract 6781: Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model

作者: Heller, Bianca ; Carrera, Lilian Martinez ; Lamfried, Katharina ; Poeckel, Daniel ; Hardt, Olaf ; Siebenmorgen, Alina ; Lupar, Katharina ; Theek, Benjamin ; Bergamini, Giovanna ; Wöhle, Christian

AbstractCancer research has made significant progress in recent years, especially in the field of immunotherapy that uses immune modulators. A significant portion of these novel therapeutic strategies focuses on manipulating the tumor microenvironment (TME). The TME is a complex structure that comprises various cellular elements, including cancer cells, immune cells, and structural components, such as secreted factors and extracellular matrix proteins. However, replicating the human TME in experimental murine models has proved challenging. Therefore, researchers have started to develop ex vivo cultivation protocols of tumor tissues, particularly precision-cut slices (PCS), that offer a three-dimensional representation of the TME. It is essential to select the best culture conditions to ensure the preservation of the TME that closely resembles the in vivo conditions. To further this research, a serum-free cell culture medium has been developed to propagate primary epithelial tumor cells originating from pancreatic, renal, and ovarian tissues. The optimized media formulation was successfully employed in the derivation and expansion of tumor cell lines, sourced from both primary and xenotransplanted tumors. An additional serum-free cell culture medium has been designed to cultivate primary lung cancer cells. Suitable culturing conditions have been introduced that maintain TME composition ex vivo cultured PCS prepared from fresh non-small cell lung carcinoma (NSCLC) tissue. Lung TumorMACS Medium and a serum-containing medium were compared, and it was found that the cellular composition of PCS cultivated in Lung TumorMACS was comparable to the original composition. At the same time, PCS cultivated in Lung TumorMACS showed a lower expression of stress genes, compared to the serum-containing alternative.Citation Format: Alina Siebenmorgen, Christian Wöhle, Katharina Lamfried, Lilian Martinez Carrera, Bianca Heller, Katharina Lupar, Giovanna Bergamini, Daniel Poeckel, Olaf Hardt, Benjamin Theek. Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6781.

2023-07-25·Communications biology

Nutritional stress-induced regulation of microtubule organization and mRNP transport by HDAC1 controlled α-tubulin acetylation.

Article

作者: Hennrich, Marco L ; Ephrussi, Anne ; Wippich, Frank ; Vaishali

In response to nutritional stress, microtubules in cells of the Drosophila female germline are depleted from the cytoplasm and accumulate cortically. This triggers aggregation of mRNPs into large processing bodies (P-bodies) and oogenesis arrest. Here, we show that hyperacetylation of α-tubulin at lysine 40 (K40) alters microtubule dynamics and P-body formation. We found that depletion of histone deacetylase 1 (HDAC1) by RNAi phenocopies the nutritional stress response, causing α-tubulin hyperacetylation and accumulation of maternally deposited mRNPs in P-bodies. Through in vitro and in vivo studies, we identify HDAC1 as a direct regulator of α-tubulin K40 acetylation status. In well-fed flies, HDAC1 maintains low levels of α-tubulin acetylation, enabling the microtubule dynamics required for mRNP transport. Using quantitative phosphoproteomics we identify nutritional stress-induced changes in protein phosphorylation that act upstream of α-tubulin acetylation, including phosphorylation of HDAC1 at S391, which reduces its ability to deacetylate α-tubulin. These results reveal that Drosophila HDAC1 senses and relays the nutritional status, which regulates germline development through modulation of cytoskeleton dynamics.

100 项与 Cellzome GmbH 相关的药物交易

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100 项与 Cellzome GmbH 相关的转化医学

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