AbstractIn the tumor microenvironment, hyaluronan surrounds neighboring cells as one of the major components of the extracellular matrix and stimulates the epithelial-mesenchymal transition (EMT) of various epithelial cancer cells. However, the mechanism of how the hyaluronic network is formed by cancer cells and regulates cancer progression and metastasis has not been known in detail. Therefore, we investigated the role of the hyaluronan network built-up by cancer cells in regulating cancer progression and metastasis in the tumor microenvironment. Our study demonstrated that ZEB1, an EMT-inducing transcription factor, reconstructs the hyaluronan network to induce the expression of ITIH2, a hyaluronan-binding protein, and hyaluronic acid synthase-2 (HAS2), ZEB1 was also shown to control the isoform switching of CD44, a hyaluronan receptor. ITIH2 knockdown and HAS inhibition reduced the formation of hyaluronan cables and inhibited cancer cell migration and invasion. In addition, the treatment of a specific ITIH2 inhibitor identified through deep learning-based screening suppressed the formation of hyaluronan cables, cell migration, and metastasis. These findings suggest that targeting the hyaluronan network could be a novel strategy for suppressing lung cancer progression and metastasis in the tumor microenvironment.Citation Format: Sieun Lee, Jihye Park, Eun Ju Kim, Seongran Cho, Sungsoo Park, Jonathan M Kurie, Young-Ho Ahn. ZEB1-regulated hyaluronan network in the lung tumor microenvironment [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 4265.

2023-11-15·Journal of computational chemistry

Application of conformational space annealing to the protein structure modeling using cryo-EM maps.

Article

作者: Lee, Jooyoung ; Park, Jimin ; Joo, Keehyoung ; Joung, InSuk

Conformational space annealing (CSA), a global optimization method, has been applied to various protein structure modeling tasks. In this paper, we applied CSA to the cryo-EM structure modeling task by combining the python subroutine of CSA (PyCSA) and the fast relax (FastRelax) protocol of PyRosetta. Refinement of initial structures generated from two methods, rigid fitting of predicted structures to the Cryo-EM map and de novo protein modeling by tracing the Cryo-EM map, was performed by CSA. In the refinement of the rigid-fitted structures, the final models showed that CSA can generate reliable atomic structures of proteins, even when large movements of protein domains were required. In the de novo modeling case, although the overall structural qualities of the final models were rather dependent on the initial models, the final models generated by CSA showed improved MolProbity scores and cross-correlation coefficients to the maps. These results suggest that CSA can accomplish flexible fitting and refinement together by sampling diverse conformations effectively and thus can be utilized for cryo-EM structure modeling.

2023-04-04·Cancer Research

Abstract 5860: ZEB1-driven reconstruction of the hyaluronan network establishes a pro-metastatic microenvironment in lung adenocarcinoma

作者: Park, Jihye ; Kim, Eun Ju ; Ahn, Young-Ho ; Kurie, Jonathan M. ; Park, Sungsoo ; Lee, Sieun

AbstractHyaluronan, one of the major components of the extracellular matrix (ECM), surrounds and protects neighboring cells from diverse stresses. Hyaluronan promotes epithelial-to-mesenchymal transition (EMT) and metastasis in various epithelial cancers. However, the mechanism by which the hyaluronan network built up by cancer cells regulates cancer progression and metastasis in the tumor microenvironment has not been elucidated in detail. In this study, ITIH2, a hyaluronan-binding protein that participates in building a hyaluronan network, was confirmed to be secreted from mesenchymal-like lung cancer cells when co-cultured with cancer-associated fibroblasts. ITIH2 was transcriptionally upregulated by ZEB1, an EMT-inducing transcription factor. Hyaluronic acid synthase-2 (HAS2) was also up-regulated by ZEB1, and the expression of HAS2 and ZEB1 showed a positive correlation in the TCGA database. In addition, ZEB1 controlled alternative splicing and isoform expression of CD44, a hyaluronan receptor. Interestingly, ITIH2 knockdown and 4-methylumbelliferone (4-MU), a HAS inhibitor, reduced the formation of hyaluronan cables and inhibited the migration and invasion of lung cancer cells. Likewise, when lung cancer cells were treated with “Compound S,” an ITIH2 inhibitor predicted by a deep learning-based drug-target interaction algorithm, the formation of hyaluronan cables and cell migration were suppressed. In addition, the ITIH2 inhibitor prevented the growth of metastatic tumors in an orthotopic lung cancer mouse model. Collectively, the EMT signal controlled by ZEB1 establishes the pro-metastatic hyaluronan network in the tumor microenvironment, suggesting a novel strategy for targeting the hyaluronan network to suppress lung cancer progression and metastasis.Citation Format: Sieun Lee, Jihye Park, Eun Ju Kim, Sungsoo Park, Jonathan M. Kurie, Young-Ho Ahn. ZEB1-driven reconstruction of the hyaluronan network establishes a pro-metastatic microenvironment in lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5860.

项与 Deargen, Inc. 相关的新闻（医药）

2023-08-29

·PipelineReview

Deargen and Serengen Partner to Accelerate Drug Discovery

DORTMUND, Germany I August 28, 2023 I Serengen and Deargen are excited to announce their collaboration to accelerate the drug discovery process. This strategic partnership brings together Serengen's novel DNA encoded library (DEL) technology with Deargen's leading AI-driven drug discovery platform, known as DearDTI. The world of drug discovery is about to get a major boost as two cutting-edge technologies join forces. The integration of Serengen's unrivalled DEL technology with Deargen's leading AI platform offers many advantages over traditional drug discovery methods, including cost savings and faster lead generation while increasing effectiveness. This powerful collaboration will usher in a new era of drug discovery that will revolutionise current processes. “By integrating Deargen’s DearDTI with Serengen’s DEL technology, the hit discovery process gains a boost in diversity and accuracy,” said KilSoo Kang, CEO of Deargen. “This collaboration aims to bring enhanced efficiency and success rates in drug development, creating a synergistic effect. Both companies share the common goal of offering valuable insights to their clients, seeking innovative and efficient drug discovery solutions, and are committed to fostering ongoing collaboration between Serengen and Deargen.” “Serengen’s slogan is 'Serendipity by Design' because our technology enables a unique DEL design,” added Thorsten Genski, CEO of Serengen. “Serendipity favours the prepared mind, as history has shown time and again. Nowadays, Artificial Intelligence is capable of analysis and prediction beyond the capabilities of a trained mind. We are excited to work with Deargen because the combination of DEL technology with Artificial Intelligence is the future. It will elevate our DEL design and data analysis to the highest level.” About Deargen Inc.: Deargen is an AI-first pharmatech company dedicated to integrating AI technology and biological data together to maximise the discovery of new medicines. Its proprietary Drug-Target Interaction (DTI) platform predicts the binding affinity and activity score between a drug-target pair. This technology unlocks substantial potential in pursuing undruggable targets, thus enhancing the accessibility and cost-effectiveness of the hit discovery process. About Serengen GmbH: Serengen's mission is to accelerate hit identification and make serendipitous discovery accessible to everyone. Its services include the screening of DELs tailored to individual projects. The company's technology overcomes the limitations of traditional DEL synthesis, allowing for a different design and approach. SOURCE: Serengen

100 项与 Deargen, Inc. 相关的药物交易

登录后查看更多信息

100 项与 Deargen, Inc. 相关的转化医学

登录后查看更多信息

组织架构

使用我们的机构树数据加速您的研究。

或

查看完整样例数据

管线布局

2024年11月05日管线快照

管线布局中药物为当前组织机构及其子机构作为药物机构进行统计，早期临床1期并入临床1期，临床1/2期并入临床2期，临床2/3期并入临床3期

临床前

登录后查看更多信息

当前项目

药物(靶点)	适应症	全球最高研发状态

DGD-201	弥漫性大B细胞淋巴瘤更多	临床前
DG-ONCO-T1	肿瘤更多	临床前
Liver cancer vaccine(Optipharm/Deargen)	肝癌更多	临床前
DGP-101	肿瘤更多	临床前
DG-HF-T1	心血管疾病更多	临床前