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Now showing items 11-19 of 19
C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-ones: Studies towards the identification of potent, cell penetrant Jumonji C domain containing histone lysine demethylase 4 subfamily (KDM4) inhibitors, compound profiling in cell-based target engagement assays.
(ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER, 2019-09-01)
Residues in the histone substrate binding sites that differ between the KDM4 and KDM5 subfamilies were identified. Subsequently, a C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one series was designed to rationally exploit ...
Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers.
(AMER ASSOC CANCER RESEARCH, 2019-08-01)
It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ...
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
(NATURE PUBLISHING GROUP, 2019-06-13)
Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ...
Lipid-mRNA Nanoparticle Designed to Enhance Intracellular Delivery Mediated by Shock Waves.
(AMER CHEMICAL SOC, 2019-03-20)
Cellular membranes are, in general, impermeable to macromolecules (herein referred to as macrodrugs, e.g., recombinant protein, expression plasmids, or mRNA), which is a major barrier for clinical translation of macrodrug-based ...
PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma.
(NATURE RESEARCH, 2019-08-22)
Pediatric high-grade gliomas are among the deadliest of childhood cancers due to limited knowledge of early driving events in their gliomagenesis and the lack of effective therapies available. In this study, we investigate ...
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
(NATURE PUBLISHING GROUP, 2019-03-07)
Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...
RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2019-01-15)
PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic ...
Affibody-Based PET Imaging to Guide EGFR-Targeted Cancer Therapy in Head and Neck Squamous Cell Cancer Models.
(SOC NUCLEAR MEDICINE INC, 2019-03-01)
In head and neck squamous cell cancer, the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR monoclonal ...
Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.
(NATURE PORTFOLIO, 2019-06-12)
Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ...