A5100345051- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Bioactive Compounds and Antitumor Agents
- Quinazolinone synthesis and applications
- Click Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and biological activity
- Chronic Lymphocytic Leukemia Research
- Synthesis and bioactivity of alkaloids
- Lung Cancer Research Studies
- Curcumin's Biomedical Applications
- Radical Photochemical Reactions
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Chronic Myeloid Leukemia Treatments
- Biochemical and Molecular Research
- Retinoids in leukemia and cellular processes
- Parasites and Host Interactions
- Lymphoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Parasite Biology and Host Interactions
- Malaria Research and Control
- Synthesis and Biological Evaluation
- Fibroblast Growth Factor Research
- Advanced Breast Cancer Therapies
East China University of Science and Technology
2016-2025
State Key Laboratory of Chemical Engineering
2019-2022
State Key Laboratory of Bioreactor Engineering
2015-2018
Princess Margaret Cancer Centre
2017
University Health Network
2017
Emory University
2010-2014
Shanghai Institute of Materia Medica
2011
Chinese Academy of Sciences
2011
Based on the advantages of multitarget drugs for cancer treatment, a new class naphthalimides was designed, synthesized, and proved to inhibit topoisomerase II (topo II), induced lysosomal membrane permeabilization (LMP), ultimately caused apoptosis cell death. The majority compounds 7a−d 8a−d potently inhibited growth five tested lines with IC50 values ranging from 2 10 μM are more active than amonafide, naphthalimide that in phase III clinical trials. These were their interactions DNA...
The accuracy of traditional bischromophore-based ratiometric probes is always compromised by undesirable energy/charge transferring interactions between the internal reference moiety and sensing chromophore. In this regard, with a monochromophore system highly desirable. Herein, an unprecedented monochromophore-based probe, which consists hydrophilic backbone poly(N-vinylpyrrolidone) (PVP) single chromophore platinum(II) tetraphenylporphyrin (Pt-TPP) reported. Combination specific assembled...
Bruton's tyrosine kinase (BTK) is a therapeutic target for B-cell-driven malignancies. Most of the approved covalent BTK inhibitors are associated with treatment limitations due to off-target toxicity and drug resistance. Developing noncovalent promising strategy address unmet clinical needs. Here, novel series pyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives were designed synthesized as inhibitors. Among them, representative compound 9 exhibited potent inhibitory activity (IC50 = 21.6 nM)...
Sulfhydryl-containing proteins play critical roles in various physiological and biological processes, the activities of those have been reported to be susceptible thiol oxidation. Therefore, development protein target fluorescent probe is highly desirable. In present work, a biotinylated coumarin fluorescence "off-on" SQ for selectively detecting thiols biotin receptor-positive cancer cells was designed with 2,4-dinitrobenzenesulfony as receptor. The exhibited dramatic responses toward...
A novel series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors fibroblast growth factor receptor 1 (FGFR1) were designed synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets representative compound 2, which was subsequently validated by enzyme-linked immunosorbent assay (ELISA) for its active FGFR1 inhibition various kinases. The structure-activity relationship (SAR) analysis aided molecular docking simulation in...
FLT3 has been validated as a therapeutic target for the treatment of acute myeloid leukemia (AML). In this paper, we describe first time, pteridin-7(8H)-one scaffold potent inhibitors derived from structural optimizations on irreversible EGFR inhibitors. The representative inhibitor (31) demonstrates single-digit nanomolar inhibition against and subnanomolar KD drug-resistance mutants. profiling in vitro tumor cell lines, it shows good selectivity AML cells harboring FLT3-ITD mutations over...
EGFR-targeted inhibitors (gefitinib and erlotinib) provided an effective strategy for the treatment of non-small-cell lung cancer. However, EGFR T790M secondary mutation has become a leading cause clinically acquired resistance to these agents. Herein, on basis previously reported irreversible inhibitor (compound 9), we present structure-based design approach, which is rationalized via analyzing its binding model comparing differences gatekeeper pocket between mutant wild-type (WT) kinases....
Degradation of target proteins has been considered to be a promising therapeutic approach, but the rational design compounds for degradation remains challenge. In this study, we reasonably designed and synthesized only 10 discover effective CDK4/6 protein degraders. Among newly compounds, 7f achieved dual protein, with DC50 values 10.5 2.5 nM, respectively. Compound also exhibited inhibitory proliferative activity against Jurkat cells an IC50 value 0.18 μM. Furthermore, induced cell...
Malaria and schistosomiasis are two of the most socioeconomically devastating parasitic diseases in tropical subtropical countries. Since current chemotherapeutic options limited defective, there is an urgent need to develop novel antiplasmodials antischistosomals. Hemozoin a disposal product formed from hemoglobin digestion by some blood-feeding parasites. formation essential process for parasites detoxify free heme, which reliable therapeutic target identifying antiparasitic agents. A...
Abstract Novel carbazole aminoalcohols were designed and synthesized as anticancer agents. Among them, alkylamine‐chain‐substituted compounds showed the most promising antiproliferative activity, with IC 50 values in single‐digit micromolar range against two human tumor cell lines. Topoisomerase I (topo I) is likely to be one of targets these compounds. Results comet assays molecular docking indicate that representative may act topo poisons, causing single‐strand DNA damage by stabilizing...
The natural compound curcumin has been investigated as an anticancer agent in many cellular systems, animal models and the clinic. overriding negative characteristics of are its low solubility, weak potency poor bioavailability. We have examined efficacy mechanism action a synthetic analog, UBS109, head neck squamous cell carcinoma. By nephelometry, this analog exhibits considerably greater solubility than curcumin. Pharmacokinetic studies single oral dose UBS109 mice revealed that peak...
Epidermal growth factor receptor (EGFR) T790M acquired drug-resistance mutation has become a major clinical challenge for the therapy of non-small cell lung cancer. Here, we applied structure-guided approach on basis previous reported EGFR inhibitor (compound 9), and designed series C4-alkyl-1,4-dihydro-2H-pyrimido[4,5-d][1,3]oxazin-2-one derivatives as novel mutant-selective inhibitors. Finally, most representative compound 20a was identified, which showed high selectivity at both enzymatic...