A5045350828- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Protein Degradation and Inhibitors
- Quinazolinone synthesis and applications
- HER2/EGFR in Cancer Research
- Computational Drug Discovery Methods
- Fibroblast Growth Factor Research
- Tuberculosis Research and Epidemiology
- Click Chemistry and Applications
- Melanoma and MAPK Pathways
- Synthesis and biological activity
- Chronic Lymphocytic Leukemia Research
- Kruppel-like factors research
- Microbial Metabolic Engineering and Bioproduction
- Peptidase Inhibition and Analysis
- PI3K/AKT/mTOR signaling in cancer
- Cell Adhesion Molecules Research
- Histone Deacetylase Inhibitors Research
- Chronic Myeloid Leukemia Treatments
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Multiple Myeloma Research and Treatments
- interferon and immune responses
- Epigenetics and DNA Methylation
Jinan University
2016-2025
Chinese Academy of Sciences
2015-2024
Tianjin Institute of Industrial Biotechnology
2016-2024
Guangdong Provincial People's Hospital
2024
State Administration of Traditional Chinese Medicine of the People's Republic of China
2024
Northwestern Polytechnical University
2021-2023
Guangzhou Medical University
2023
Wuhan Institute of Virology
2023
Zhengzhou University
2023
Shanghai Institute of Materia Medica
2023
Abstract Acetyl-CoA is a fundamental metabolite for all life on Earth, and also key starting point the biosynthesis of variety industrial chemicals natural products. Here we design construct Synthetic (SACA) pathway by repurposing glycolaldehyde synthase acetyl-phosphate synthase. First, engineer to improve catalytic activity more than 70-fold, condense two molecules formaldehyde into one glycolaldehyde. Second, repurpose phosphoketolase convert acetyl-phosphate. We demonstrated feasibility...
Bcr-AblT315I mutation-induced imatinib resistance remains a major challenge for clinical management of chronic myelogenous leukemia (CML). Herein, we report GZD824 (10a) as novel orally bioavailable inhibitor against broad spectrum Bcr-Abl mutants including T315I. It tightly bound to Bcr-AblWT and with Kd values 0.32 0.71 nM, respectively, strongly inhibited the kinase functions nanomolar IC50 values. The compound potently suppressed proliferation Bcr-Abl-positive K562 Ku812 human CML cells...
Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh 7rj) inhibited the enzymatic activity DDR1, with IC50 values 6.8 7.0 nM, respectively, but were significantly less potent in suppressing kinase activities DDR2, Bcr-Abl, c-Kit. Further study revealed...
The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying activity. Utilizing 1 a lead molecule, we successfully designed synthesized series of 1H-1,2,3-triazole-4-carboxamide new A agents. One the most potent compounds, 3b, inhibited replication various H3N2 H1N1 strains with IC50 values ranging from 0.5 to 4.6 μM. Compound 3b also strongly H5N1 (RG14),...
Taxus, commonly known as yew, is a well-known gymnosperm with great ornamental and medicinal value. In this study, by assembling chromosome-level genome of the Himalayan yew (Taxus wallichiana) 10.9 Gb in 12 chromosomes, we revealed that tandem duplication acts driving force gene family evolution genome, resulting main genes for paclitaxel biosynthesis, i.e. those encoding taxadiene synthase, P450s, transferases, being clustered on same chromosome. The may also provide genetic resources...
Template-free enzymatic approaches are considered the most promising solution for next-generation artificial DNA synthesis. However, development of these technologies has been hampered by lack efficient enzymes specialized stepwise nucleotide addition. By combining evolutionary analysis, high-throughput mutagenesis scanning, and rational design, we identified a terminal deoxynucleotidyl transferase from Zonotrichia albicollis (ZaTdT) reshaped its catalytic cavity to better accommodate...
A series of pyrazolo[1,5-a]pyridine-3-carboxamide derivatives were designed and synthesized as new anti-Mycobacterium tuberculosis (Mtb) agents. The compounds exhibit promising in vitro potency with nanomolar MIC values against the drug susceptive H37Rv strain a panel clinically isolated multidrug-resistant Mtb (MDR-TB) strains. One representative (5k) significantly reduces bacterial burden an autoluminescent H37Ra infected mouse model, suggesting its potential to be lead compound for future...
Respiration is a promising target for the development of new antimycobacterial agents, with growing number compounds in clinical entering this space. However, more candidate inhibitors are needed to expand therapeutic options available drug-resistant Mycobacterium tuberculosis infection. Here, we characterize putative respiratory complex III (QcrB) inhibitor, TB47: pyrazolo[1,5-a]pyridine-3-carboxamide. TB47 active (MIC between 0.016 and 0.500 μg/mL) against panel 56 M. isolates, including...
The EGFR(T790M) mutant contributes approximately 50% to clinically acquired resistance against gefitinib or erlotinib. However, almost all the single agent clinical trials of second generation irreversible EGFR inhibitors appear inadequate overcome EGFR(T790M)-related resistance. We have designed and synthesized a series 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidinyl derivatives as novel inhibitors. most potent compounds, 2q 2s, inhibited enzymatic activities wild-type mutated EGFRs, with...
EGFRC797S mutation inducing resistance against third generation EGFR inhibitor drugs is an emerging "unmet clinical need" for nonsmall cell lung cancer patients. The pyrimidopyrimidinone derivative JND3229 was identified as a new highly potent with single digit nM potency. It also exhibited good in vitro and vivo monodrug anticancer efficacy xenograft mouse model of BaF3/EGFR19D/T790M/C797S cells. A high-resolution X-ray crystallographic structure determined to elucidate the interactions...
A series of 2-amino-2,3-dihydro-1H-indene-5-carboxamides were designed and synthesized as new selective discoidin domain receptor 1 (DDR1) inhibitors. One the representative compounds, 7f, bound with DDR1 a Kd value 5.9 nM suppressed kinase activity an half-maximal (50%) inhibitory concentration 14.9 nM. 7f potently inhibited collagen-induced signaling epithelial–mesenchymal transition, dose-dependently colony formation pancreatic cancer cells, exhibited promising in vivo therapeutic...
Tertiary C797S mutation of epidermal growth factor receptor (EGFR)-mediated resistance in non-small-cell-lung-cancer (NSCLC) patients is still an unmet clinical need. Several classes adenosine 5′-triphosphate-competitive or allosteric EGFRT790M/C797S inhibitors and degraders have been developed, but none them received approval from the regulatory agencies. Herein, we report structure-based design conformational constrained 4-(1-ethylsufonyl-3-indolyl)-2-phenylaminopyrimidines as new by using...
MET alterations have been validated as a driven factor in NSCLC and gastric cancers. The c-Met inhibitors, capmatinib, tepotinib, savolitinib, are only approved for the treatment of harboring exon 14 skipping mutant MET. We used molecular hybridization conjunction with macrocyclization strategy structural optimization to obtain series 2-(2-(quinolin-6-yl)ethyl)pyridazin-3(2H)-one derivatives new inhibitors. One macrocyclic compounds, D6808, potently inhibited kinase MET-amplified Hs746T...