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Biochemistry & Molecular Biology
Shuchi Goyal, Manjinder Singh, Divya Thirumal, Pratibha Sharma, Somdutt Mujwar, Krishna Kumar Mishra, Thakur Gurjeet Singh, Ravinder Singh, Varinder Singh, Tanveer Singh, Sheikh F. Ahmad
Summary: Alzheimer's disease is caused by plaque agglomeration and entanglement in neural cells, leading to apoptosis. Current research is focused on GSK-3 inhibitor analogues for potential treatment advancements.
Article
Biochemistry & Molecular Biology
Xiaochang Liu, Jiaxue Yu, Yongyan Luo, Haojian Dong
Summary: This study successfully identified small molecules that inhibit GSK-3 beta activity, and demonstrated their drug-like properties. Two of the compounds showed significant inhibitory activity and can be potential leads for developing GSK-3 beta inhibitors.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Review
Biochemistry & Molecular Biology
Beatrice Balboni, Mirco Masi, Walter Rocchia, Stefania Girotto, Andrea Cavalli
Summary: Most kinase inhibitors target ATP-binding sites, resulting in promiscuity and potential off-target effects. Allostery provides an alternative approach to achieve selectivity, but its exploitation is challenging due to diverse mechanisms and long-range conformational effects. GSK-3 beta, a critical target involved in multiple pathologies, shares a highly homologous ATP-binding site with other kinases. Allostery offers the potential for selective and moderate inhibition, which is desirable for GSK-3 beta. However, the development of allosteric inhibitors for GSK-3 beta has been limited, with only one reaching clinical trials, and there are no X-ray structures of GSK-3 beta with allosteric inhibitors in the PDB data bank.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Lynette Steele, Aarren J. Mannion, Gary Shaw, Kenneth A. Maclennan, Graham P. Cook, Christopher E. Rudd, Alison Taylor
Summary: GSK-3 plays a crucial role in T cell function and tumor immunity, with the isoforms GSK-3α and GSK-3β having differential effects on immune responses and tumor infiltration, working together to control PD-1 expression and tumor growth.
Article
Biochemistry & Molecular Biology
Beatrice Balboni, Shailesh Kumar Tripathi, Marina Veronesi, Debora Russo, Ilaria Penna, Barbara Giabbai, Tiziano Bandiera, Paola Storici, Stefania Girotto, Andrea Cavalli
Summary: In this study, we identified promising GSK-3 beta inhibitors through 1D F-19 NMR fragment screening and biophysical assays. We also proposed an alternative screening workflow to overcome the limitations of common GSK-3 beta inhibitors and found selective inhibitors and/or inhibitors capable of modulating GSK-3 beta activity without complete inhibition.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Bhanwar Singh Choudhary, Sukanya, Pakhuri Mehta, Stephane Bach, Sandrine Ruchaud, Thomas Robert, Beatrice Josselin, Slawomir Filipek, Ruchi Malik
Summary: The study identified new GSK-3 beta inhibitors with potential in Alzheimer's disease pathology, among which ZINC09036109 showed promising selectivity and strong binding affinity with GSK-3 beta.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Medicinal
Weiping Lyu, Qihang Li, Qi Li, Ying Chen, Yingming Wang, Tongzhong Tang, Feng Feng, Heng Chi, Yuan Li, Wenyuan Liu, Haopeng Sun
Summary: In this study, new GSK-3 beta inhibitors were identified through pharmacophore-based virtual screening. Four compounds showed inhibitory activity, with compounds 6 and 9 demonstrating good safety profiles. Compound 8 was identified as the preferred lead molecule for further development in treating Alzheimer's disease.
MOLECULAR INFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Wagdy M. Eldehna, Sara T. Al-Rashood, Tarfah Al-Warhi, Razan O. Eskandrani, Amal Alharbi, Ahmed M. El Kerdawy
Summary: In this study, three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3 beta inhibitors targeting breast cancer. The N-1 -unsubstituted oxindole derivatives showed potent cytotoxic activity, while the N-1-substituted derivatives exhibited moderate to weak activity on breast cancer cell lines. The most potent compounds caused cell cycle arrest in the G2/M phase by inhibiting CDK2/GSK-3 beta, as demonstrated by enzyme inhibition assays and molecular docking studies.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2021)
Article
Dermatology
Qi Jia, Li Tao, Yinyin Zhou, Li Song, Zhonghong Wei, Tao Lu, James R. Woodgett, Yin Lu
Summary: The study found that the GSK-3 inhibitor Pym-5 can delay the growth of melanoma cells, promote melanin production, and achieve this effect by activating the Wnt/β-Catenin signaling pathway.
JOURNAL OF DERMATOLOGICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Davoud Ghazanfari, Mahboubeh S. Noori, Stephen C. Bergmeier, Jennifer Hines, Kelly D. McCall, Douglas J. Goetz
Summary: COB-187 inhibits GSK3 beta via a specific, reversible, time and Cys-199-dependent mechanism, demonstrating high selectivity and potent activity against the target enzyme.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Chengqian Wei, Junjie Huang, Yu Wang, Yifang Chen, Xin Luo, Shaobo Wang, Zengxue Wu, Jixiang Chen
Summary: A series of new oxadiazole sulfone derivatives containing an amide moiety were synthesized to screen high-efficiency antibacterial agents for rice bacterial diseases. Compound 10 showed excellent antibacterial activity against Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola, with EC50 values superior to commercial bactericides. Compound 10 demonstrated superior protective and curative activities against rice bacterial leaf blight and rice bacterial leaf streak compared to other tested compounds. Additionally, compound 10 exhibited potential mechanisms of action by affecting extracellular polysaccharides, cell membranes, and enzyme activity of dihydrolipoamide S-succinyltransferase to inhibit the growth of Xanthomonas oryzae pv. oryzae and Xanthomonas oryzae pv. oryzicola.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Meiling Shen, Lingfeng Li, Yue Li, Xi Gu, Longhui Bai, Chengfeng Xia, Wenyong Xiong, Zhili Zuo
Summary: This study conducted virtual screening of over 1.5 million molecules from the Chemdiv database to identify potential inhibitors of hTRPC5. The screening process evaluated the affinities of the candidates and assessed their inhibitory effects on Ca2+ influx. Two molecules, SML-1 and SML-13, showed significant inhibition of intracellular Ca2+ levels and could potentially be lead compounds for the development of therapeutics targeting hTRPC5 and its associated physiological activities and diseases.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sukanya Sukanya, Bhanwar Singh Choudhary, Pakhuri Mehta, Slawomir Filipek, Ruchi Malik
Summary: Alzheimer's Disease is a significant disease affecting the aging population and is challenging to develop drugs due to blood-brain barrier permeation. This study performed virtual screening on a compound library and identified 10 potential compounds with favorable ADME profiles. In vitro studies revealed a compound with high GSK-3β inhibition and selectivity. Additionally, a potent and selective CK1ε inhibitor was discovered.
MEDICINAL CHEMISTRY RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Shivani Chandel, Rajveer Singh, Anupam Gautam, Velayutham Ravichandiran
Summary: The study demonstrates that gedunin may act as an effective GSK-3 beta inhibitor for the management of neuroblastoma by inducing apoptosis and inhibiting cell proliferation. Further preclinical and clinical investigation is needed to validate these findings.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Chemistry, Physical
Alfredo Rus, Victor M. Bolanos-Garcia, Agatha Bastida, Paula Morales
Summary: This study utilizes virtual screening and molecular docking to identify potential HPSE inhibitors that may have therapeutic potential in treating chronic and infectious diseases.