A5100382709- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Cell death mechanisms and regulation
- Pancreatitis Pathology and Treatment
- Pancreatic and Hepatic Oncology Research
- Apelin-related biomedical research
- Microtubule and mitosis dynamics
- Drug Transport and Resistance Mechanisms
- Immune cells in cancer
- Macrophage Migration Inhibitory Factor
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Computational Drug Discovery Methods
- Acute Lymphoblastic Leukemia research
- Molecular Sensors and Ion Detection
- Nuclear Receptors and Signaling
- Synthesis and Reactivity of Heterocycles
- Erythrocyte Function and Pathophysiology
- Catalytic C–H Functionalization Methods
- Melanoma and MAPK Pathways
- Luminescence and Fluorescent Materials
- interferon and immune responses
- Pancreatic function and diabetes
University of North Carolina at Chapel Hill
2016-2025
Huazhong Agricultural University
2024-2025
Segeberger Kliniken
2025
UNC Lineberger Comprehensive Cancer Center
2025
Northern Jiangsu People's Hospital
2016-2025
Suzhou Institute of Biomedical Engineering and Technology
2020-2025
Southeast University
2025
Chinese Academy of Sciences
2020-2025
University of Science and Technology of China
2020-2025
Guangdong Medical College
2024
MolProbity is a general-purpose web server offering quality validation for 3D structures of proteins, nucleic acids and complexes. It provides detailed all-atom contact analysis any steric problems within the molecules as well updated dihedral-angle diagnostics, it can calculate display H-bond van der Waals contacts in interfaces between components. An integral step process addition full optimization all hydrogen atoms, both polar nonpolar. New functions have been added RNA, interfaces, NMR...
Significance This study indicates that a subpopulation of tumor cells expresses both PD-1 and PD-L1, which decreases the growth by suppressing canonical signaling pathways, i.e. AKT ERK1/2 pathways. In absence adaptive immune system, cell-intrinsic PD-1/PD-L1 mediates resistance to treatment with FDA-approved anti-PD-1/PD-L1 antibodies activating ERK1/2. These findings provide an additional explanation for cancer immunotherapy.
Mitophagy plays a crucial role in maintaining intracellular homeostasis through the removal of dysfunctional mitochondria and recycling their constituents lysosome-degradative pathway, which leads to microenvironmental changes within mitochondria, such as pH, viscosity, polarity. However, most mitochondrial fluorescence viscosity probes only rely on electrostatic attraction readily leak out from during mitophagy with decreased membrane potential, thus easily leading an inaccurate detection...
We previously reported a potent small molecule Mer tyrosine kinase inhibitor UNC1062. However, its poor PK properties prevented further assessment in vivo. report here the sequential modification of UNC1062 to address DMPK and yield new highly orally bioavailable inhibitor, 11, capable inhibiting phosphorylation vivo, following oral dosing as demonstrated by pharmaco-dynamic (PD) studies examining phospho-Mer leukemic blasts from mouse bone marrow. Kinome profiling versus more than 300...
Metastatic melanoma is one of the most aggressive forms cutaneous cancers. Although recent therapeutic advances have prolonged patient survival, prognosis remains dismal. C-MER proto-oncogene tyrosine kinase (MERTK) a receptor with oncogenic properties that often overexpressed or activated in various malignancies. Using both protein immunohistochemistry and microarray analyses, we demonstrate MERTK expression correlates disease progression. was highest metastatic melanomas, followed by...
Myeloid cell receptor tyrosine kinases TYRO3, AXL, and MERTK their ligands, GAS6 PROTEIN S, physiologically suppress innate immune responses, including in the tumor microenvironment. Here, we showed that myeloid-derived suppressor cells (MDSC) dramatically upregulated ligands [monocytic MDSCs (M-MDSC)>20-fold, polymorphonuclear (PMN-MDSC)>15-fold] tumor-bearing mice. from Mertk-/-, Axl-/- , Tyro3-/- mice exhibited diminished suppressive enzymatic capabilities, displayed deficits T-cell...
A versatile Cu-catalyzed cross-coupling reaction to various unsymmetrical disulfanes has been presented, from phthalimide-carried disulfur transfer reagents and commercially available boronic acids under mild practical conditions. The method features the unprecedented use of disulfurating (Harpp reagent) in chemistry is highlighted by broad substrate scopes, even applicable for aryl-disulfur moieties (ArSS−). Notably, robustness this methodology shown late-stage modification bioactive...
The pyrrole moiety is an important structural motif in functional materials, natural products, and pharmaceuticals. More more synthetic strategies toward pyrroles have emerged, where various efficient building blocks are developed these synthons enable the syntheses of with different numbers components. However, no review specifically summarizes according to type number employed blocks. To aid researchers design appropriate substrates for synthesis, herein we summarized advances classified...
Flavonoids are a class of polyphenolic compounds widely present in the diet and herbal products. The interactions flavonoids with some major efflux transporters [e.g., P-glycoprotein, multidrug resistance-associated protein 1 (MRP1), breast cancer resistance protein] have been reported; however, their uptake largely unknown. Organic anion-transporting polypeptide OATP1B1 is liver-specific transporter important hepatic drug disposition. Our objective was to evaluate effects 20 naturally...
// Xiao-Dong Wang 1 , Jian-Jun Qian Dou-Sheng Bai Zhen-Nan Li Guo-Qing Jiang and Jie Yao Department of Hepatobiliary Pancreatic Surgery, Clinical Medical College Yangzhou University, Subei People’s Hospital Jiangsu Province, Yangzhou, Republic China Correspondence to: Yao, email: Keywords : pancreatic cancer, marital status, SEER, survival analysis Received November 28, 2015 Accepted March 07, 2016 Published 29, Abstract Marital status is an independent prognostic factor for in several...
Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase triggers efferocytosis can suppress innate immune responses. The aim study was to define MerTK as therapeutic target using an orally bioavailable inhibitor, UNC2025.We examined expression in tumor cells matched patient GBM samples by double-label immunohistochemistry. UNC2025-induced inhibition studied vitro vivo.MerTK/CD68+ increased...
MERTK is ectopically expressed and promotes survival in acute lymphoblastic leukemia (ALL) cells thus a potential therapeutic target. Here we demonstrate both direct effects of inhibition on induction anti-leukemia immunity via suppression the coinhibitory PD-1 axis. A MERTK-selective tyrosine kinase inhibitor, MRX-2843, mediated immunocompromised mice bearing MERTK-expressing human xenograft. In addition, host by genetic deletion (Mertk-/- mice) or treatment with MRX-2843 significantly...
FMS-like tyrosine kinase 3-targeted (FLT3-targeted) therapies have shown initial promise for the treatment of acute myeloid leukemia (AML) expressing FLT3-activating mutations; however, resistance emerges rapidly. Furthermore, limited options exist FLT3-independent AML, demonstrating need novel that reduce toxicity and improve survival. MERTK receptor is overexpressed in 80% to 90% AMLs contributes leukemogenesis. Here, we describe MRX-2843, a type 1 small-molecule inhibitor abrogates...
Abstract Purpose: MERTK tyrosine kinase is ectopically expressed in 30% to 50% of acute lymphoblastic leukemias (ALL) and more than 80% myeloid (AML) a potential therapeutic target. Here, we evaluated the utility UNC2025, inhibitor, for treatment leukemia. Experimental Design: Preclinical vitro vivo assays using cell lines primary leukemia patient samples were used evaluate antileukemic effects UNC2025. Results: UNC2025 potently inhibited prosurvival signaling, induced apoptosis, reduced...
Abstract Isocitrate dehydrogenase 1 and 2 (IDH1 IDH2) are key metabolic enzymes that mutated in a variety of cancers to confer gain-of-function activity resulting the accumulation an oncometabolite, D-2-hydroxyglutarate (2-HG). Accumulation 2-HG can result epigenetic dysregulation block cellular differentiation, suggesting these mutations play role neoplasia. Based on its potential as cancer target, number small molecule inhibitors have been developed specifically inhibit mutant forms IDH...
CDK9 inhibitors may treat KRAS-mutant cancers by inducing MYC protein degradation.
Main observation and conclusion Elucidating the intrinsic relationship between viscosity/H 2 O mitochondria‐associated diseases remains a great challenge owing to lack of research on multiple models, such as inflammation malignant tumor models. In this work, we have developed mitochondria‐specific orange/near‐infrared‐emissive fluorescent probe TTPB, for dual‐imaging viscosity H levels in two different channels. The exhibited remarkable response with NIR emission round 666 nm, was highly...
Background Physical activity (PA) is important for health. However, there little evidence on how weight stigma, time spent sedentary activities (including smartphone, social media, online learning), outdoor activity, and nomophobia associate with PA among Chinese individuals consideration of gender. The present study examined the aforementioned associations in COVID-19 pandemic era. Methods University students ( N = 3,135; 1,798 females, 1,337 males) a mean age 19.65 years SD 2.38) completed...
Breast cancer resistance protein (BCRP/ABCG2) is an ATP-binding cassette efflux transporter, important in drug disposition and the development of multidrug cancer. Flavonoids, a large class natural compounds widely present diet herbal products, have been shown vitro to be BCRP inhibitors. The flavonoid chrysin potent inhibitor BCRP, inhibiting mitoxantrone with IC<sub>50</sub> 0.39 μM BCRP-overexpressing human MCF-7 breast cells. purpose this study was investigate potential pharmacokinetic...
Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, kinase inhibitors may promote leukemic cell death further act as chemosensitizers increasing efficacy reducing toxicities of current ALL regimens. We have applied a structure-based design approach discover novel small molecule inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit activity at sub-nanomolar...
Abnormal activation or overexpression of Mer receptor tyrosine kinase has been implicated in survival signaling and chemoresistance many human cancers. Consequently, is a promising novel cancer therapeutic target. A structure-based drug design approach using pseudo-ring replacement strategy was developed validated to discover new family pyridinepyrimidine analogues as potent inhibitors. Through SAR studies, 10 (UNC2250) identified the lead compound for further investigation based on high...
Abstract Purpose: The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-dependent HER dimer signaling. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, antitumor activity of MEHD7945A. Experimental Design: Patients with locally advanced or metastatic epithelial tumors received escalating doses (1–30 mg/kg) every 2 weeks (q2w) until disease progression intolerable toxicity. An expansion cohort was enrolled at recommended II...