A5040980276- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Prostate Cancer Diagnosis and Treatment
- Prostate Cancer Treatment and Research
- Peptidase Inhibition and Analysis
- Axial and Atropisomeric Chirality Synthesis
- Synthesis of Indole Derivatives
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Liver physiology and pathology
- Immune cells in cancer
- Lung Cancer Treatments and Mutations
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Alkaloids: synthesis and pharmacology
- Renal cell carcinoma treatment
- Chemical Synthesis and Analysis
- RNA regulation and disease
- HER2/EGFR in Cancer Research
- Acute Myeloid Leukemia Research
- Multiple Myeloma Research and Treatments
- Biochemical and Molecular Research
- Cancer therapeutics and mechanisms
- Catalytic C–H Functionalization Methods
- Protein Degradation and Inhibitors
State Key Laboratory of Natural Medicine
2021-2025
China Pharmaceutical University
2021-2025
Changhai Hospital
2015-2023
Yahoo (United Kingdom)
2023
Shanghai Changzheng Hospital
2023
Second Military Medical University
2015-2023
Shandong University
2020-2021
Xuzhou Medical College
2016-2018
BGI Group (China)
2017
China National GeneBank
2017
Abstract A direct and enantioselective oxidative cross‐coupling of racemic 2,2‐diarylacetonitriles with electron‐rich (hetero)arenes has been described, which allows for efficient construction triarylmethanes bearing all‐carbon quaternary stereocenters excellent chemo‐ enantioselectivity. The reaction an functional group tolerance, exhibits a broad scope respect to both 2,2‐diarylacetonitrile (hetero)arene components. rich chemistry the cyano facile synthesis other valuable chiral centers...
Osimertinib resistance is an unmet clinical need for the treatment of non-small cell lung cancer (NSCLC), and main mechanism tertiary C797S mutation epidermal growth factor receptor (EGFR). To date, there no inhibitor approved Osimertinib-resistant NSCLC. Herein, we reported a series derivatives as fourth-generation inhibitors which were rationally designed. Top candidate D51 potently inhibited EGFRL858R/T790M/C797S mutant with IC50 value 14 nM suppressed proliferation H1975-TM cells nM,...
The epidermal growth factor receptor (EGFR) tertiary C797S mutation is an important cause of resistance to Osimertinib, which seriously hinders the clinical application Osimertinib. Developing proteolysis-targeting chimeras (PROTACs) targeting EGFR mutants can offer a promising strategy overcome drug resistance. In this study, some novel PROTACs were designed and synthesized based on new inhibitor displayed potent degradation effect in H1975-TM cells harboring EGFRL858R/T790M/C797S....
A cross-dehydrogenative coupling (CDC) strategy for enantioselective access to acyclic CF<sub>3</sub>-substituted all-carbon quaternary stereocenters has been established.
Targeting c-Met is a clinical trend for the precise treatment of HCC, but potential issue acquired drug resistance cannot be ignored. Targeted protein degradation technology has demonstrated promising prospects in disease and overcoming due to its special mechanism action. In this study, we designed synthesized two series novel degraders conducted systematic biological evaluation optimal compound H11. H11 exhibited good activity anti-HCC activity. Importantly, also more potent inhibitory...
MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, it is a target for treatment breast cancer. In this study, we identified synthesized series novel small-molecule inhibitors PPI. The representative compound C19 showed potent activity against PPI with IC50 487 ± 99 nM tight binding to SND1-purified protein Kd value 279 17 nM. Compound significantly degraded SND1 downregulated downstream at level. Further biological evaluations...
Peptide deformylase (PDF) is a metalloprotease catalyzing the removal of formyl group from newly synthesized proteins, which makes it an important antibacterial drug target. Given importance PDF inhibitors like actinonin in discovery, several reported potent were used to develop pharmacophore models using Galahad module Sybyl 7.1 software. Generated composed two donor atom centers, four acceptor centers and hydrophobic groups. Model-1 was screened against Zinc database compounds retrieved as...
Cigarette smoking has been investigated as a major risk factor for renal cell carcinoma (RCC). 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one of the most abundant carcinogenic N -nitrosamines present in cigarette smoke. However, association between repair capacity NNK-induced DNA damage and RCC remains unknown. We used comet assay to assess whether sensitivity NNK precursor 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc) induced damage, which partly reflects...
Epidermal growth factor receptor (EGFR)-activating mutation is an important oncogenic driver of nonsmall cell lung cancer (NSCLC) patients. Osimertinib has been the first-line treatment for EGFR-mutated NSCLC. However, tertiary C797S leads to resistance by blocking covalent binding Cys797 Osimertinib. To date, there are no approved inhibitors resistance. Herein, we identified a novel lead compound S8 targeting EGFRL858R/T790M/C797S structure-based virtual screening and synthesized series...
An asymmetric 1,6-conjugate addition to presynthesized δ-aryl-δ-cyano-disubstituted para-quinone methides through bifunctional phosphonium-amide-promoted ion-pair catalysis for acyclic all-carbon quaternary stereocenter construction has been described. Both and cyclic 1,3-dicarbonyls participate in the alkylation reaction, furnishing a wide array of diarylmethanes bearing single carbon or vicinal stereocenters with high efficiency excellent stereoselectivity. Computational studies elucidate...
Abstract Acute myeloid leukemia (AML) is a fatal disease characterized by bleak prognosis. For over four decades, treatment options for AML have been constrained to administering high-dose cytotoxic chemotherapy. However, the emergence of drug resistance and resultant toxic side effects created an urgent necessity identifying novel therapeutic targets. In this study, non-receptor protein tyrosine phosphatase type 2 (PTPN2) highly expressed in AML. Remarkably, knock down PTPN2 expression...
In recent years, Staphylococcus aureus have developed resistance to medicines used for the treatment of human infections. Therefore, search antibacterial agents high potency against is great concern. Peptide deformylase (PDF), a metalloprotease catalyzing removal formyl group from newly synthesized proteins, has been considered be an important drug target.To discover novel drugs based on peptide deformylase.PDF-based virtual screening compounds Traditional Chinese Medicine Database@Taiwan...
Human peptide deformylase (HsPDF) is an important target for anticancer drug discovery. In view of the limited HsPDF, inhibitors were reported, and high-throughput virtual screening (HTVS) studies based on HsPDF developing new PDF remain to be reported. We reported here diverse small molecule with excellent activities designed HTVS molecular docking using crystal structure HsPDF. The compound M7594_0037 exhibited potent against HeLa, A549 MCF-7 cell lines IC50s 35.26, 29.63 24.63 μM,...
Abstract A direct and enantioselective oxidative cross‐coupling of racemic 2,2‐diarylacetonitriles with electron‐rich (hetero)arenes has been described, which allows for efficient construction triarylmethanes bearing all‐carbon quaternary stereocenters excellent chemo‐ enantioselectivity. The reaction an functional group tolerance, exhibits a broad scope respect to both 2,2‐diarylacetonitrile (hetero)arene components. rich chemistry the cyano facile synthesis other valuable chiral centers...
Phosphoinositide-3-kinase (PI3K) overexpressed in many tumors is a promising target for cancer therapy. However, due to toxicity from the ubiquitous expression of PI3K tissues, development inhibitors with high selectivity and low has become an urgent need tumor treatment. Herein, based on HipHop, we designed synthesized series 6-(4,6-dimorpholino-1,3,5-triazin-2-yl)benzo[d]oxazol-2-amine derivatives as potent, selective, long-acting PI3Kα inhibitors. Compound 27 was determined potent...
Renal cancer is a common malignancy of the urinary system, and renal clear cell carcinoma (RCCC) most pathological type. Transmembrane channel-like (TMC) protein an evolutionarily conserved gene family containing 8 members, however there still lack comprehensive analysis about TMC members in RCCC. In this study, we analyzed expression RCCC from TCGA investigated prognosis values immune infiltration We found that TMC2, TMC3, TMC5, TMC7 TMC8 were significantly related with overall survival...
Abstract Despite initial response to androgen signaling therapy, most prostate cancer (PCa) patients eventually relapse and remain incurable. ADAR1-mediated A-to-G editing plays oncogenic roles in various tumors. However, the specific function of ADAR1 global RNA edited targets governing PCa progression underexplored. Here, we demonstrate that highly expressed as a crucial target PCa, develop novel small-molecule inhibitor ZYS-1 with significant anti-tumor efficacy favorable safety profile....