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We have designed and synthesized a novel series of 2,8-diaryl-quinoxalines as Janus kinase 2 inhibitors. Many of the inhibitors show low nanomolar activity against JAK2 and potently suppress proliferation of SET-2 cells in vitro. In addition, compounds from this series have favorable rat pharmacokinetic properties suitable for in vivo efficacy evaluation.
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http://dx.doi.org/10.1016/j.bmcl.2010.02.056 | DOI Listing |
RSC Chem Biol
July 2025
Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University Max-von-Laue-Str. 9 D-60438 Frankfurt am Main Germany
Herein we present the rapid development of LH168, a potent and highly selective chemical probe for WDR5, streamlined by utilizing a DEL-ML (DNA encoded library-machine learning) hit as the chemical starting point. LH168 was comprehensively characterized in bioassays and demonstrated potent target engagement at the WIN-site pocket of WDR5, with an EC of approximately 10 nM, a long residence time, and exceptional proteome-wide selectivity for WDR5. In addition, we present the X-ray co-crystal structure and provide insights into the structure-activity relationships (SAR).
View Article and Find Full Text PDFDiabetes Obes Metab
September 2025
School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
Aim: To estimate the healthcare and economic burden associated with improved risk factor control for people with type 2 diabetes in Hong Kong over 10 years.
Materials And Methods: We obtained population-based data from electronic healthcare records of the Hong Kong Hospital Authority. Risk factor targets were defined by American Diabetes Association guidelines.
Adv Sci (Weinh)
September 2025
China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Immune Response and Immunotherapy, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, GIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research Centre, GIBH-CUHK Joint Resea
TP53 mutations are highly associated with hepatocellular carcinoma (HCC), a common and deadly cancer. However, few primary drivers in the progression of HCC with mutant TP53 have been identified. To uncover tumor suppressors in human HCC, a genome-wide CRISPR/Cas9-based screening of primary human hepatocytes with MYC and TP53 overexpression (MT-PHHs) is performed in xenografts.
View Article and Find Full Text PDFACS Omega
September 2025
Centre of Artificial Intelligence Driven Drug Discovery, Faculty of Applied Science, Macao Polytechnic University, Macao SAR 999078, China.
Tyrosinase, a copper-dependent oxidase, plays a critical role in melanin biosynthesis and is a target in skin-whitening cosmetics. Conventional inhibitors like arbutin and kojic acid are widely used but suffer from cytotoxicity, instability, and inconsistent efficacy, highlighting the need for safer, more effective alternatives. In this study, two ligand-based machine learning models were developed: one to predict the biological activity of compounds and the other to estimate specific pIC values.
View Article and Find Full Text PDFSAR QSAR Environ Res
August 2025
Laboratory of Drug Design and Discovery, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Evaluating the permeability of different molecular structures across the Caco-2 cell line is crucial for drug discovery and development. The present study primarily focuses on developing machine learning-based multiclass classification models for predicting the permeability of molecules across the Caco-2 cell line. However, the class imbalance in permeability datasets poses a significant challenge for developing predictive models in the case of multiclass analysis.
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