A5100732191- Cancer therapeutics and mechanisms
- HIV/AIDS drug development and treatment
- Nuclear Receptors and Signaling
- Acute Myeloid Leukemia Research
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Chronic Lymphocytic Leukemia Research
- Bioactive Compounds and Antitumor Agents
- Cytokine Signaling Pathways and Interactions
- Cancer Genomics and Diagnostics
- DNA and Nucleic Acid Chemistry
- Biochemical and Molecular Research
- Computational Drug Discovery Methods
- Synthesis of Tetrazole Derivatives
- Chemical Reactions and Isotopes
- Carcinogens and Genotoxicity Assessment
- CRISPR and Genetic Engineering
- Synthesis and Biological Evaluation
- Chronic Myeloid Leukemia Treatments
- Click Chemistry and Applications
- PI3K/AKT/mTOR signaling in cancer
- Metal complexes synthesis and properties
- Synthesis and Reactivity of Heterocycles
- Fungal Infections and Studies
- Antimicrobial Resistance in Staphylococcus
Xingtai People's Hospital
2015
Hebei Medical University
2015
In this article, we describe the first outbreak of Candida parapsilosis fungemia in our hospital. We examined a cluster four nosocomial cases C. that occurred neonatal intensive care unit (NICU) Affiliated Xingtai People's Hospital Hebei Medical University over two-week period. ascertained patient parameters including clinical characteristics, blood and sputum cultures, drug sensitivity test results. Cultures from eight samples obtained infected preterm infants showed identical...
DNA-dependent protein kinase (DNA-PK), a driver of the non-homologous end-joining (NHEJ) DNA damage response pathway, plays an instrumental role in repairing double-strand breaks (DSB) induced by DNA-damaging poisons. We evaluate ZL-2201, orally bioavailable, highly potent, and selective pharmacologic inhibitor DNA-PK activity, for treatment human cancerous malignancies. ZL-2201 demonstrated greater selectivity effectively inhibited autophosphorylation concentration- time-dependent manner....
<p>ZL-2201 anti-proliferative IC50s and ATM mutational VAF status</p>
<p>Phenotypic effects of combining ZL-2201 and Doxorubicin</p>
<p>ZL-2201 treatment exhibits potent antitumor efficacy in vivo.</p>
<p>ZL-2201 treatment exhibits potent antitumor efficacy in vivo.</p>
<p>ZL-2201 reduces DNA damage-induced MCM2 phosphorylation (Ser108).</p>
<p>Kinetics of Bleomycin-induced DNA-PK phosphorylation by ZL-2201</p>
<p>ZL-2201 anti-proliferative IC50s and ATM mutational VAF status</p>
<div>Abstract<p>DNA-dependent protein kinase (DNA-PK), a driver of the non-homologous end-joining (NHEJ) DNA damage response (DDR) pathway, plays an instrumental role in repairing double-strand breaks (DSBs) induced by DNA-damaging poisons. We evaluate ZL-2201, orally bioavailable, highly potent, and selective pharmacological inhibitor DNA-PK activity, for treatment human cancerous malignancies. ZL-2201 demonstrated greater selectivity effectively inhibited autophosphorylation...
<p>Synthesis of ZL-2201</p>
<div><p>DNA-dependent protein kinase (DNA-PK), a driver of the non-homologous end-joining (NHEJ) DNA damage response pathway, plays an instrumental role in repairing double-strand breaks (DSB) induced by DNA-damaging poisons. We evaluate ZL-2201, orally bioavailable, highly potent, and selective pharmacologic inhibitor DNA-PK activity, for treatment human cancerous malignancies. ZL-2201 demonstrated greater selectivity effectively inhibited autophosphorylation concentration-...
<p>Phenotypic effects of combining ZL-2201 and Doxorubicin</p>
<p>Synthesis of ZL-2201</p>
<p>ZL-2201 reduces DNA damage-induced MCM2 phosphorylation (Ser108).</p>
<p>Kinetics of Bleomycin-induced DNA-PK phosphorylation by ZL-2201</p>
<p>Cellular efficacy of ZL-2201 across cancer cell lines</p>
<p>Supplementary Methods</p>
<p>Supplementary Methods</p>
<p>Cellular efficacy of ZL-2201 across cancer cell lines</p>
<p>Cellular efficacy of ZL-2201 across cancer cell lines</p>
<p>Phosphoproteomic screen identifies MCM2 Ser108 phosphorylation decreased by ZL-2201. <b>A,</b> Simple Western showing inhibition of pDNA-PK upon treatment with PRKDC siRNA, 300 nmol/L and 3.5 μmol/L ZL-2201 ± 10 bleomycin used in phospho-MS analysis. <b>B,</b> The Venn diagram phosphoproteins ATM DNA-PK substrate motifs + siRNAs at the indicated timepoints. <b>C,</b> validation pMCM2 (S108) NCI-H1703 cells. <b>D,</b> (5 mg/kg) tumor...
<p>Evaluation of ZL-2201 antiproliferative activity <i>in vitro</i>. <b>A,</b> Chemical structure ZL-2201, a potent and selective DNA-PK inhibitor. <b>B,</b> Concentration-dependent response to in M059J M059K glioblastoma cancer cells measured by CTG after 6-day treatment. The graph represents the average inhibitory (IC<sub>50</sub>) values (<i>n</i> = 3). <b>C,</b> CRISPR KO ATM A549 FaDu 6 days 2–5)....
<p>ZL-2201 treatment exhibits potent antitumor efficacy in vivo.</p>
<p>ZL-2201 anti-proliferative IC50s and ATM mutational VAF status</p>