A5049953201- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Microtubule and mitosis dynamics
- Radiopharmaceutical Chemistry and Applications
- Cancer Treatment and Pharmacology
- Cancer therapeutics and mechanisms
- FOXO transcription factor regulation
- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Biochemical and Molecular Research
- Endoplasmic Reticulum Stress and Disease
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Retinoids in leukemia and cellular processes
- GDF15 and Related Biomarkers
- Adenosine and Purinergic Signaling
- Lung Cancer Treatments and Mutations
- Cancer Cells and Metastasis
- Neuroblastoma Research and Treatments
- Autophagy in Disease and Therapy
- Mechanisms of cancer metastasis
- Macrophage Migration Inhibitory Factor
Nerviano Medical Sciences
2014-2025
MPS1 kinase is a key regulator of the spindle assembly checkpoint (SAC), mitotic mechanism specifically required for proper chromosomal alignment and segregation. It has been found aberrantly overexpressed in wide range human tumors necessary tumoral cell proliferation. Here we report identification characterization NMS-P715, selective orally bioavailable small-molecule inhibitor, which selectively reduces cancer proliferation, leaving normal cells almost unaffected. NMS-P715 accelerates...
Abstract The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority cancers and its activity strongly contributes to tumour initiation progression. Inactivation PIN1 function conversely curbs growth cancer stem cell expansion, restores chemosensitivity blocks metastatic spread, thus providing rationale for therapeutic strategy based on inhibition. Notwithstanding, potent inhibitors are still missing from arsenal anti-cancer drugs. By...
Polo-like kinase 1 (PLK1) is a serine/threonine protein considered to be the master player of cell-cycle regulation during mitosis. It indeed involved in centrosome maturation, bipolar spindle formation, chromosome separation, and cytokinesis. PLK1 overexpressed variety human tumors its overexpression often correlates with poor prognosis. Although five different PLKs are described humans, depletion or inhibition activity sufficient induce arrest apoptosis cancer cell lines xenograft tumor...
ALK is a tractable antibody-drug conjugate target in neuroblastoma.
Maternal embryonic leucine zipper kinase (MELK) is upregulated in several types of tumor, including breast, prostate, and brain tumors. Its expression generally associated with cell survival, proliferation, resistance to apoptosis. Therefore, the potential MELK inhibitors as therapeutic agents recently attracting considerable interest. Here we report first structures complex AMP-PNP nanomolar inhibitors. Our studies shed light on role UBA domain, provide a characterization active site,...
Theranostic RGD-camptothecin conjugates, possessing a disulfide linker and fluorescent naphthalimide moiety, were synthesized biologically evaluated. The conjugates showed nanomolar affinity for the purified αVβ3-integrin receptor. For antiproliferative assays, U87 human glioblastoma chosen as αVβ3-expressing cells, whereas non clone (U87 β3-KO) was generated negative control. Although β3-KO cells treated with statistically significant reduced fluorescence intensity (in range 7–12 %)...
Abstract First generation of antibody drug conjugates (ADCs) for anticancer therapy has been described more than two decades ago with gemtuzumab-ozogamicin receiving the first approval in 2000. Over last 4 years, 8 new ADCs got FDA essentially due to innovation on linker improving disposition patients and manufacturability together technical advantages engineering biologics introduction cytotoxic payloads such as deruxtecan. In future, next will be developed exploring beyond currently used...
New antibodies-drug conjugate (ADC) payloads overcoming chemoresistance and killing also poorly proliferating tumors at well-tolerated doses are much desired. Duocarmycins a well-known class of highly potent cytotoxic agents, with DNA minor groove-binding alkylation properties, active in chemoresistant tumors. Although different duocarmycin derivatives have been used during the years as for ADC production, unfavorable physicochemical properties impaired production ADCs optimal features....
At the onset of proteomic studies protein samples have to be accurately separated by two dimensional electrophoresis (2-DE); subsequently polypeptides are identified. Grape tissues, in particular roots, can very problematic due their hardness and high content compounds that interfere classical extraction. We used a phenol-based extraction method presence protease inhibitor Polyvinylpolypyrrolidone (PVPP). In this paper we demonstrate gives satisfactory reproducible separation allowing...
Abstract Thienoindoles are a new proprietary class of highly potent DNA minor groove alkylating agents. This is characterized by fused thiophene ring whose intrinsic electron-withdrawing character provides nearly optimal increase in stability and potency subunits. Furthermore, the presence solubilizing moiety on portion compounds with physicochemical properties compatible deployment as antibody payloads. Extensive optimization this has led to identification toxin NMS-P528 sub-nanomolar IC50...
Abstract The rapidly growing field of Antibody-Drug Conjugates (ADCs) has recently spurred the study novel drug payloads. In particular, much interest been paid to identification cytotoxic agents, which differ in mechanism from anti-tubulin currently most commonly employed class for ADC coupling. Novel payloads ADC-based therapy should thus ideally possess highly potent activity with a diverse tubulin as well physicochemical properties, facilitate coupling antibodies. Duocarmycins are...
Abstract Activated ALK by mutation or amplification is a validated therapeutic target in subset of patients with high-risk neuroblastoma, and tyrosine kinase inhibitors are being developed to abrogate signaling (Bresler et al, 2014). Native expressed on the surface majority neuroblastoma tumors, but not normal tissue, giving it properties tumor antigen. We hypothesized that ALK-targeted antibodies may be useful as single-agent immunotherapy combination small-molecule - especially where...
Abstract Valosin Containing Protein (VCP), also called p97 in mammals and cdc48 yeast, is an ubiquitously expressed essential AAA ATPase important specific cellular processes including Endoplasmic Reticulum Associated Degradation (ERAD), Golgi reformation, membrane fusion autophagy. VCP a hexameric complex formed by six identical protomers, each composed of three domains: N-terminal domain responsible for the interaction with co-factors adaptor proteins, two domains, D1 D2. acts as...
Abstract Antibody-drug conjugates (ADCs) are increasingly employed in different oncology settings with more than forty products clinical evaluation at present, and two approved drugs, ado-trastuzumab emtansine brentuximab vedotin, respectively targeting Her2 CD30 positive tumors. Although many antibody targets have been so far considered for this approach, only a handful of toxins exploited, 50% ADCs result to be conjugated well known tubulin binding agents, auristatin maitansine. New...
Supplementary Figures 1-14, Tables 1-4, Methods, References from Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase
Supplementary Figures 1-14, Tables 1-4, Methods, References from Targeting the Mitotic Checkpoint for Cancer Therapy with NMS-P715, an Inhibitor of MPS1 Kinase
<p>PDF file - 1.2MB</p>
<p>PDF file - 213K</p>
<p>NMS-P945 stability in plasma</p>