Article
Chemistry, Medicinal
Li -An Shen, Xinyan Peng, Ya Bao, Chenglong Liu, Hao Zhang, Jianqi Li, Di Zhu, Qingwei Zhang
Summary: The study found that quercetin and its derivatives have potential inhibitory effects on the /9-catenin/BCL9 protein-protein interaction, which is involved in cancer development. The compound C1 showed the strongest inhibitory effect by directly binding to /9-catenin and disrupting its interaction with BCL9.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Victor Quereda, Sylvia M. Frydman, Qianqian Ming, Vincent C. Luca, Derek R. Duckett, Haitao Ji
Summary: This study introduces a drug-like small molecule, ZW4864, which selectively disrupts the protein-protein interaction between BCL9 and beta-catenin, effectively suppressing beta-catenin signaling activation and target gene expression in a mouse model. This provides a potential therapeutic target for developing drugs targeting aberrant Wnt/beta-catenin signaling in diseases such as cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Hyeryon Lee, Kyung-Hwa Baek, Trong-Nhat Phan, I. Seul Park, Sangchul Lee, Jiho Kim, Joo Hwan No
Summary: This study identified a potential drug target for visceral leishmaniasis and identified small molecule inhibitors with anti-leishmanial activity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Maria Mushtaq Ali, Sehrish Naz, Sajda Ashraf, Stefan Knapp, Zaheer Ul-Haq
Summary: BRD9 inhibitors have potential therapeutic value in cancer treatment by selectively targeting BRD9 and BRD7 proteins, regulating chromatin structure and gene expression, and inhibiting tumor growth and progression.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Harriet M. Thompson, Haitao Ji
Summary: A series of new small-molecule beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction inhibitors were reported. Among them, compound 21 showed potent inhibition in cellular context and demonstrated higher potential in regulating transcription and expression of beta-catenin target genes and suppressing survival of beta-catenin-dependent cancer cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Heqi Sun, Jianmin Wang, Hongyan Wu, Shenggeng Lin, Junwei Chen, Jinghua Wei, Shuai Lv, Yi Xiong, Dong-Qing Wei
Summary: This study proposes a deep learning framework called MultiPPIMI for predicting the interaction between PPI targets and modulators. Experimental results show that MultiPPIMI performs well in predicting both cold-start scenarios and random-split scenarios, and can assist in screening inhibitors for Keap1/Nrf2 PPI interactions.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Multidisciplinary Sciences
Joo-Leng Low, Weina Du, Tenzin Gocha, Gokce Oguz, Xiaoqian Zhang, Ming Wei Chen, Srdan Masirevic, Daniel Guo Rong Yim, Iain Bee Huat Tan, Adaikalavan Ramasamy, Hao Fan, Ramanuj DasGupta
Summary: A molecular docking-based approach was used to identify small molecules targeting the beta-catenin (beta-cat)-TCF4 protein-protein interaction (PPI) in the nuclear Wnt signaling pathway. In vitro experiments confirmed that GB1874 is an effective inhibitor of the Wnt pathway, impacting proliferation and stemness in colorectal cancer cells. In vivo studies demonstrated that GB1874 inhibited the growth of colorectal cancer tumor xenografts, showing potential for therapeutic development against Wnt-associated cancer indications.
Review
Chemistry, Medicinal
Zhen Wang, Zilu Li, Haitao Ji
Summary: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with cancer, and direct targeting of beta-catenin is a promising strategy but challenging. Research has identified potential small-molecule binding sites and summarized bioactive small molecules that target beta-catenin directly.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Multidisciplinary Sciences
Jie Zhong, Yuegui Guo, Shaoyong Lu, Kun Song, Ying Wang, Li Feng, Zhen Zheng, Qiufen Zhang, Jiacheng Wei, Peng Sang, Yan Shi, Jianfeng Cai, Guoqiang Chen, Chen-Ying Liu, Xiuyan Yang, Jian Zhang
Summary: This study identifies a best-in-class inhibitor for the protein-protein interaction crucial to colorectal cancer metastasis and develops a sensitivity-enhanced tracer for fluorescence polarization assays to accurately detect high-activity inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Katrin S. Eckhardt, Theresa Muenzel, Julian Graeb, Thorsten Berg
Summary: STAT5a and STAT5b are constitutively active transcription factors in many human tumors. The development of resorcinol bisphosphate to Stafiba, a phosphatase-stable inhibitor of both STAT5a and STAT5b with activity in the low micromolar concentration range, provides insights into the structure-activity relationships of resorcinol bisphosphates and their potential as inhibitors of both STAT5a and STAT5b.
Review
Biochemistry & Molecular Biology
Sailan Shui, Stephen Buckley, Leo Scheller, Bruno E. Correia
Summary: Small-molecule responsive protein switches are important tools for controlling cellular processes, and recent advances in computational protein design have led to the development of switches that can respond to a wider range of small-molecule inducers with more sophisticated mechanisms.
Review
Chemistry, Medicinal
Hao Zhang, Ya Bao, Chenglong Liu, Jianqi Li, Di Zhu, Qingwei Zhang
Summary: The Wnt/β-catenin signaling pathway plays a crucial role in organism development and disease, making the direct targeting of protein-protein interactions a promising strategy for pathway inhibition. Despite the early stage of research in this area, there is hope for future development of inhibitors.
FUTURE MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hao Zhang, Chenglong Liu, Qiushi Chen, Li-An Shen, Wenting Xiao, Jiayi Li, Yonghui Wang, Di Zhu, Qingwei Zhang, Jianqi Li
Summary: Direct disruption of the fi-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential strategy for colorectal cancer (CRC) treatment through inhibiting oncogenic Wnt activity. In this study, a series of 3-phenylpiperidine derivatives were synthesized and evaluated as fi-catenin/BCL9 PPI inhibitors. Compound 41 showed the best inhibitory activity, selectively inhibiting the growth of CRC cells and downregulating oncogenic Wnt target gene expression.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Marianna Nalli, Domiziana Masci, Andrea Urbani, Giuseppe La Regina, Romano Silvestri
Summary: This review discusses the recent advances in small molecule beta-catenin agents, including the structure-activity relationships and biological activities of inhibitors, providing useful knowledge for the discovery of therapeutic beta-catenin drugs for cancer treatment.
Article
Multidisciplinary Sciences
Helen Tanton, Tomasz Sewastianik, Hyuk-Soo Seo, David Remillard, Roodolph St Pierre, Pratyusha Bala, Daulet Aitymbayev, Peter Dennis, Keith Adler, Ezekiel Geffken, Zoe Yeoh, Nicholas Vangos, Filip Garbicz, David Scott, Nilay Sethi, James Bradner, Sirano Dhe-Paganon, Ruben D. Carrasco
Summary: The study identified a specific small-molecule inhibitor that can suppress Wnt/beta-catenin signaling and slow down the growth of colorectal cancer. This finding is of great significance for the development of novel therapies for colorectal cancer.
Article
Chemistry, Organic
Xiaowei Wu, Haitao Ji
JOURNAL OF ORGANIC CHEMISTRY
(2018)
Article
Chemistry, Organic
Xiaowei Wu, Haitao Ji
ORGANIC & BIOMOLECULAR CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Jin Wang, Haitao Ji
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
Peng Sang, Min Zhang, Yan Shi, Chunpu Li, Sami Abdulkadir, Qi Li, Haitao Ji, Jianfeng Cai
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Qingliang Li, Rezaul M. Karim, Mo Cheng, Mousumi Das, Lihong Chen, Chen Zhang, Harshani R. Lawrence, Gary W. Daughdrill, Ernst Schonbrunn, Haitao Ji, Jiandong Chen
Review
Chemistry, Medicinal
Zhen Wang, Zilu Li, Haitao Ji
Summary: Aberrant activation of the Wnt/beta-catenin signaling pathway is associated with cancer, and direct targeting of beta-catenin is a promising strategy but challenging. Research has identified potential small-molecule binding sites and summarized bioactive small molecules that target beta-catenin directly.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Narges K. Tafreshi, Darpan N. Pandya, Christopher J. Tichacek, Mikalai M. Budzevich, Zhen Wang, Jordan N. Reff, Robert W. Engelman, David C. Boulware, Alberto A. Chiappori, Jonathan R. Strosberg, Haitao Ji, Thaddeus J. Wadas, Ghassan El-Haddad, David L. Morse
Summary: The study demonstrates significant potential for the clinical translation of [Ac-225]Ac-DOTA-TATE for lung NENs, showing notable tumor growth delay and prolonged time to experimental endpoint.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Wen Luo, Yongqiang Zhang, Haitao Ji
Summary: The study presents a new small-molecule inhibitor that selectively disrupts the beta-catenin/BCL9 interaction, inhibits the role of the Wnt signaling pathway in cancer, and can serve as a lead compound for further optimization.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Victor Quereda, Sylvia M. Frydman, Qianqian Ming, Vincent C. Luca, Derek R. Duckett, Haitao Ji
Summary: This study introduces a drug-like small molecule, ZW4864, which selectively disrupts the protein-protein interaction between BCL9 and beta-catenin, effectively suppressing beta-catenin signaling activation and target gene expression in a mouse model. This provides a potential therapeutic target for developing drugs targeting aberrant Wnt/beta-catenin signaling in diseases such as cancer.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Zilu Li, Min Zhang, Kevin B. Teuscher, Haitao Ji
Summary: Structure-based design and optimization led to the discovery of a small-molecule beta-catenin/BCL9 inhibitor ZL3138, which disrupts the protein-protein interaction effectively and selectively in living cells, showing potential anti-tumor activity.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Tao Xiao, Luxin Sun, Min Zhang, Zilu Li, Eric B. Haura, Ernst Schonbrunn, Haitao Ji
Summary: A monocarboxylic inhibitor was designed and synthesized to disrupt the protein-protein interaction between GRB2 and phosphotyrosine-containing proteins. Biochemical studies showed compound 7 binds with the SH2 domain of GRB2 with higher potency, while X-ray crystallographic studies revealed key structural features for GRB2-inhibitor binding. This compound with a -1 formal charge offers a new direction for generating cell-permeable inhibitors for the aberrant Ras-MAPK signaling cascade.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Zhen Wang, Haitao Ji
Summary: The cooperativity index, Kc, was developed to examine the binding synergy between hot spots of the ligand-protein. The spatial arrangements of hydrophilic alpha-helical hot spots in protein-protein interaction (PPI) complex structures were disclosed and quantified using novel clustering models. The driving force for the convergence of these hot spots was analyzed, allowing the development of pharmacophore models for designing new mimetics.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Zhen Wang, Min Zhang, Harriet M. Thompson, Haitao Ji
Summary: A series of new small-molecule beta-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction inhibitors were reported. Among them, compound 21 showed potent inhibition in cellular context and demonstrated higher potential in regulating transcription and expression of beta-catenin target genes and suppressing survival of beta-catenin-dependent cancer cells.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Shelby R. Kell, Zhen Wang, Haitao Ji
Summary: Fragment-based ligand discovery (FBLD) is a successful approach for designing small-molecule protein-protein interaction (PPI) inhibitors. This article describes a computational protocol using fragment hopping for developing small-molecule PPI inhibitors and includes a case study to illustrate its efficiency. Fragment hopping enables the design of PPI inhibitors based solely on key binding features in the PPI complex structure. This approach is an open system that can incorporate different programs and software to improve its performance.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)