A5068757483- Cancer, Lipids, and Metabolism
- Metal complexes synthesis and properties
- Microtubule and mitosis dynamics
- Colorectal Cancer Treatments and Studies
- Metal-Catalyzed Oxygenation Mechanisms
- Cancer-related Molecular Pathways
- Cancer Mechanisms and Therapy
- Chronic Lymphocytic Leukemia Research
- Ferroptosis and cancer prognosis
- Lymphoma Diagnosis and Treatment
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Biochemical and Molecular Research
- Ubiquitin and proteasome pathways
- Cancer Treatment and Pharmacology
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Multiple Myeloma Research and Treatments
- Melanoma and MAPK Pathways
- ATP Synthase and ATPases Research
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Treatments and Mutations
- Cancer therapeutics and mechanisms
- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
Ono Pharmaceutical (United States)
2012-2023
Research & Development Institute
2014-2023
Merck (Germany)
2020
Institut Curie
2012
Sorbonne Paris Cité
2012
Hôpital Saint-Louis
2012
Hôpital René Huguenin
2012
Université Paris Cité
2012
Inserm
2012
Centre National de la Recherche Scientifique
2012
Gemcitabine, a nucleoside analogue, is an important treatment for locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC) but provides only modest survival benefit. Targeting downstream effectors of the RAS/ERK signaling pathway by direct inhibition MEK1/2 proteins promising therapeutic strategy, as aberrant activation this occurs frequently in PDAC. In study, ability pimasertib, selective allosteric inhibitor, to enhance gemcitabine efficacy was tested molecular mechanism...
This phase I, open-label, dose-escalation study evaluated the safety, pharmacokinetics and pharmacodynamics of combination therapy with HDM2 inhibitor SAR405838 MEK1/2 pimasertib administered orally once daily (QD) or twice (BID) in locally advanced metastatic solid tumours (NCT01985191). Patients documented wild-type TP53 RAS RAF mutations were enroled. A 3 + design was employed. The primary objective to assess maximum tolerated dose (MTD). Twenty-six patients treated 200 300 mg QD plus 60...
// Francesca Vena 1, * , Ruochen Jia Arman Esfandiari 1 Juan J. Garcia-Gomez Manuel Rodriguez-Justo 2 Jianguo Ma 3 Sakeena Syed Lindsey Crowley Brian Elenbaas Samantha Goodstal John A. Hartley and Daniel Hochhauser Cancer Research UK Drug-DNA Interactions Group, UCL Institute, Paul O'Gorman Building, University College London, London WC1E 6DD, Department of Pathology, EC1M6BQ, EMD Serono Development Billerica 01821, MA, USA These authors have contributed equally to this work Correspondence...
Triple-negative breast cancers (TNBC) have an aggressive phenotype with a relatively high rate of recurrence and poor overall survival. To date, there is no approved targeted therapy for TNBCs. Aurora kinases act as regulators mammalian cell division. They are important cell-cycle progression frequently overexpressed or mutated in human tumors, including cancer. In this study, we investigated the therapeutic potential targeting preclinical models using pan-inhibitor kinases, AS703569. vitro,...
TL-895 (formerly known as M7583) is a potent, highly selective, adenosine triphosphate (ATP)-competitive, second-generation, irreversible inhibitor of Bruton's tyrosine kinase (BTK). We characterized its biochemical and cellular effects in vitro vivo models. was evaluated preclinically for potency against BTK using IC50 concentration-response curves; selectivity 270-kinase panel; phosphorylation Ramos Burkitt's lymphoma cells by ProteinSimple Wes analysis one study; anti-proliferative...
Triple-negative breast cancer (TNBC) is a major cause of death among patients that results from intrinsic and acquired resistance to systemic chemotherapies.To identify novel targets for effective treatment TNBC through combination strategies with MEK inhibitor (AS703026), we used method combining high-throughput two-and three-dimensional (2D 3D) RNAi screening.TNBC cells were transfected kinome siRNA library comprising targeting 790 kinases under both 2D 3D culture conditions or without...
ABL tyrosine kinase inhibitors (TKI) like Imatinib, Dasatinib and Nilotinib are the gold standard in conventional treatment of CML. However, emergence resistance remains a major problem. Alternative therapeutic strategies TKI-resistant CML urgently needed. We asked whether dual inhibition BCR-ABL Aurora kinases A-C could overcome mediated by mutations. therefore tested PHA-739358 R763/AS703569 Ba/F3- cells ectopically expressing wild type (wt) or mutants. show that both compounds exhibited...
Abstract Pimasertib (AS-703026) is a potent and highly selective ATP noncompetitive MEK1/2 inhibitor that has shown anti-tumor activity in different pre-clinical models. We have previously reported pimasertib as single agent lymphoma models preliminary combinations results (Gaudio et al, AACR 2014). Here, we report detailed data on of with the PI3K-delta idelalisib BTK-inhibitor ibrutinib. Methods. Cell lines derived from activated B-cell like (ABC) diffuse large (DLBCL) (OCI-Ly10, TMD8),...
Abstract MSC2015103 is an orally bio-available, selective, and highly potent small molecule inhibitor of MEK1/2. As a follower to the front-runner MEK inhibitor, pimasertib (MSC1936369/AS703026), prime objective for program differentiate two compounds. Results from previous pharmacokinetic (PK) studies in mice had shown that both compounds could effectively cross blood-brain barrier, but was retained brain longer than pimasertib. This further confirmed study examining whole-body distribution...
Abstract Low-grade serous ovarian carcinoma is a distinct neoplasm from high-grade and chemo-resistant, both in the first line setting as well subsequent lines of therapy. Serous tumors low malignant potential grade cancer (LGSOC) appear to be dependent, part, on activation mitogen-activated protein kinase (MAPK) survival signaling pathway, furthermore display significantly higher prevalence KRAS or BRAF mutations contrast carcinomas. The PI3K/AKT/mTOR Ras/Raf/MEK/ERK pathways are...
Abstract Treatment of patients with lymphomas resistant/refractory to standard chemotherapy is challenging. Development and identification new compounds targeting components relevant pathways needed. Pimasertib a potent highly selective ATP noncompetitive MEK1/2 inhibitor, which has been shown able induce G1 cell cycle arrest apoptosis in different pre-clinical cancer models antitumor activity xenograft mainly BRAF KRAS activating mutations. Here, we report data on the evaluation pimasertib...
Abstract The efficacy and tolerability of the MEK inhibitor Pimasertib hypoxia-activated prodrug TH-302 combination were explored in pancreatic biliary tract preclinical tumor xenograft models. These studies based on hypotheses that may occur by several possible mechanisms including inhibition DNA repair or increase hypoxia Pimasertib, differential targeting oxic hypoxic compartments respectively. Since had each been tested separate clinical trials cancer with gemcitabine (NCT01016483...
<p>Figure S5.A. Inhibition of tumor growth in mice treated with 15mg/kg pimasertib plus 80mg/kg gemcitabine.</p>
<p>Figure S2.B. RRM1 expression is not modulated by EGFR signalling.</p>
<p>Figure S1.B. Apoptotic effect of simultaneous administration pimasertib with gemcitabine.</p>
<p>Figure S2.A. MEK inhibitor AS703988 induces downregulation of RRM1 protein Immunoblotting analysis expression</p>
<p>supplementary figure legend</p>