A5084826357- HER2/EGFR in Cancer Research
- Monoclonal and Polyclonal Antibodies Research
- Radiopharmaceutical Chemistry and Applications
- Cancer therapeutics and mechanisms
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Cell Adhesion Molecules Research
- Cancer Immunotherapy and Biomarkers
- Estrogen and related hormone effects
- Advanced Breast Cancer Therapies
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Cannabis and Cannabinoid Research
- Cancer Treatment and Pharmacology
- Protein Degradation and Inhibitors
- Heme Oxygenase-1 and Carbon Monoxide
- Cell Image Analysis Techniques
- Single-cell and spatial transcriptomics
- Cyclopropane Reaction Mechanisms
- Ferroptosis and cancer prognosis
- Thyroid Cancer Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Innovative Microfluidic and Catalytic Techniques Innovation
Nerviano Medical Sciences
2011-2025
This work takes advantage of one the hallmarks cancer, that is, presence tumor infiltrating cells immune system and leukocyte-secreted enzymes, to promote activation an anticancer drug at site. The peptidomimetic integrin ligand cyclo(DKP-RGD) was found accumulate on surface αv β3 integrin-expressing human renal cell carcinoma 786-O cells. conjugated paclitaxel through a Asn-Pro-Val (NPV) tripeptide linker, which is substrate neutrophil-secreted elastase. In vitro linker cleavage assays...
// Maria Chiara Anania 1, * , Fabio Gasparri 2, Elena Cetti 1 Ivan Fraietta 2 Katia Todoerti 3 Claudia Miranda Mara Mazzoni Re Riccardo Colombo Giorgio Ukmar Stefano Camisasca Sonia Pagliardini Marco A. Pierotti 4 Antonino Neri 5, 6 Arturo Galvani Angela Greco Molecular Mechanisms Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Cell Biology Department, Nerviano Medical Sciences Srl, (MI), Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer...
Herein we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin α
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 %)...
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....
The identification of drugs capable reactivating γ-globin to ameliorate β-thalassemia and Sickle Cell anemia is still a challenge, as available inducers have limited clinical indications. High-throughput screenings (HTS) aimed identify new potentially therapeutic require suitable first-step-screening methods combining the possibility detect variation in γ/β globin ratio with robustness cell line. We took advantage K562 line variant expressing β-globin (β-K562) set up multiplexed high-content...
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 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...
Abstract FMS-like tyrosine kinase 3 (FLT3) and KIT are both members of the class III receptor family characterized by an autoinhibitory juxtamembrane (JM) domain that docks with to stabilize a catalytically inactive conformation. Therefore, mutations or deletion in this adjacent regions cause constitutive activation these kinases as observed 30% AML patients for FLT3 70% adult GIST subset melanoma KIT. NMS-P948 is alkoxy-indazole derivative potent dual inhibitor (IC50 26 89 nM,...
<p>NMS-P945 stability in plasma</p>
<p>NMS-P945 trastuzumab ADC PK data</p>
<div>Abstract<p>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...
<p>Half-life determination of NMS-P528 +self immolative spacer at different pH and timepoints</p>
<p>Biochemical characterization of trastuzumab conjugated to MMAE and Deruxtecan</p>
<p>Payload antiproliferative activity</p>
<p>Antiproliferative activity of NMS-P528, MMAE, DXd and doxorubicin in parental MDR expressing cell lines</p>
<p>Payload antiproliferative activity</p>
<p>Cell lines used in the study with providers, date of master banking and growth media compositions</p>
<p>Stability of NMS-P528 in mouse, rat, monkey and human plasma</p>
<div>Abstract<p>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...
<p>NMS-P945 stability in plasma</p>
<p>NMS-P945 trastuzumab ADC PK data</p>