A5083376922- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Neuroendocrine Tumor Research Advances
- Liver physiology and pathology
- Adenosine and Purinergic Signaling
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Pharmacogenetics and Drug Metabolism
- Pancreatic and Hepatic Oncology Research
- Enzyme function and inhibition
- Chemical Reactions and Isotopes
- Pancreatic function and diabetes
- TGF-β signaling in diseases
- FOXO transcription factor regulation
- Cancer Mechanisms and Therapy
- Nanoplatforms for cancer theranostics
- Heat shock proteins research
- Cancer and biochemical research
- Caveolin-1 and cellular processes
- Lung Cancer Treatments and Mutations
- Neuropeptides and Animal Physiology
- Protein Tyrosine Phosphatases
- Organ Transplantation Techniques and Outcomes
- PI3K/AKT/mTOR signaling in cancer
- Signaling Pathways in Disease
Merck (Germany)
2013-2023
Abstract Purpose: The mesenchymal–epithelial transition factor (c-Met) receptor, also known as hepatocyte growth receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation associated with variety of human malignancies including cancers the lung, kidney, stomach, liver, brain. In this study, we investigated properties two novel compounds developed to selectively inhibit in antitumor therapeutic...
Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring exon 14 (METex14) skipping mutations. Examining treatment-naive or tepotinib-resistant cells with amplification METex14 mutations identifies other receptor tyrosine kinases (RTKs) that co-exist in prior to tepotinib exposure and become more prominent upon resistance. In a small cohort of patients genetic alterations treated tepotinib, gene copy number gains RTKs were found at baseline...
Abstract Introduction M8891 is a selective and reversible inhibitor of methionine aminopeptidase 2 (MetAP2). We describe translational research to define the target pharmacokinetics (PK) associated pharmacodynamic (PD) levels, which were used support efficacious dose selection in humans. Methods In vitro vivo PK characteristics investigated animal species, data integrated using vitro–in correlation allometric methods predict clearance, volume distribution, absorption parameters parallel,...
Abstract N-terminal processing by methionine aminopeptidases (MetAP) is a crucial step in the maturation of proteins during protein biosynthesis. Small-molecule inhibitors MetAP2 have antiangiogenic and antitumoral activity. Herein, we characterize structurally novel inhibitor M8891. M8891 potent, selective, reversible small-molecule blocking growth human endothelial cells differentially inhibiting cancer cell growth. A CRISPR genome-wide screen identified tumor suppressor p53 MetAP1/MetAP2...
<p>Body weight curves for RCC PDX model RXF-2796-bearing mice treated with vehicle, M8891 (100 mg/kg, daily, per os), sunitinib (40 or the combination are shown</p>
<p>Protein identification: stained bands (upper and lower) were excised, trypsin in-gel digested, analyzed by peptide mapping using MALDI MS</p>
<p>EF1a-1 knockdown (96 hours) in A549 or HCT116 cancer cells, which were treated for 24 hours with DMSO 1E−07 M of M8891 and analyzed the presence MetEF1a-1 by Simple Western using generated rabbit monoclonal antibody MKV-3-165-11.</p>
<p>Body weight curves of colon cancer PDX model CXF-1783-bearing mice treated with vehicle or M8891 (150 mg/kg, twice daily, per os) monotherapy</p>
<p>Body weight curves of gastric cancer PDX model GXF-1172-bearing mice treated with vehicle or M8891 (150 mg/kg, twice daily, per os) as monotherapy</p>
<p>Description of effect M8891 on HUVEC formation 3D Matrigel methodology</p>
<p>Description of effect M8891 on HUVEC formation 3D Matrigel methodology</p>
<p>Generation of rabbit monoclonal antibody against unprocessed human EF1a</p>