Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 184 for “"Kinase Inhibitors"”.
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Tyrosine Kinase Inhibitors in Triple Negative Breast Cancer
… was to assess the potential role of selected inhibitors in TNBC, including the small molecule tyrosine kinases inhibitors of EGFR gefitinib and erlotinib, the monoclonal antibody against EGFR cetuximab, and the multi-target tyrosine kinase inhibitor dasatinib. Significantly higher EGFR …
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CNS Penetration of Tyrosine Kinase Inhibitors in Mouse Models
… (PDGFR), crenolanib, as examples of tyrosine kinase inhibitors currently tested for treatment of malignant glioma. Given the poor microdialysis probe recovery of these lipophilic molecules, we enhanced their recovery by including an affinity-based trapping agent, 10% …
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Functionalization and Modification of Naphthaquinone Analogs as HER2 Kinase Inhibitors
… breast cancer. We are developing small molecule inhibitors that bind to the ATP binding site of the tyrosine kinase domain in order to inhibit tyrosine auto-phosphorylation. This process controls biological pathways that mediate the cell growth. In normal cells this process is highly controlled. …
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Design, synthesis, and biological evaluation of selective sphingosine kinase inhibitors
Sphingosine kinase (SphK) has emerged as an attractive target for cancer therapeutics due to its role in cell proliferation. SphK phosphorylates sphingosine to form sphingosine-1-phosphate (S1P) which has been implicated as a major player in cancer growth and survival. SphK exists as two different …
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Structure Activity Relationship Studies on Isoform Selective Sphingosine Kinase Inhibitors
… is catalyzed by the two isoforms of sphingosine kinase (SphK1 and SphK2). Therefore, SphKs are a potential therapeutic target; however, the physiological role of SphK2 is still emerging. In order to determine the role of SphK2 in vivo, more potent and selective small molecule inhibitors of SphK2, …
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SYNTHETIC AND MECHANISTIC STUDIES OF PRECIOUS METAL-MODIFIED TYROSINE KINASE INHIBITORS
Molecularly targeted therapies such as tyrosine kinase inhibitors (TKIs) make up an important class of oncology drugs. Targeting of cancer cells harboring oncogenic molecular targets, especially signaling kinases, with precision medicines, while sparing the majority of normal healthy cells, has led …
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Synthesis and evaluation of novel kinase inhibitors as anti-cancer agents
Disruption of protein kinase signalling pathways is often associated with cancer. TheRhoA/ROCK kinase pathway has been shown to be constitutively expressed in many cancersand has also been shown to be involved in metastasis and apoptosis. ROCK is inhibited bythe ATP mimic Y27632, which …
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Near Infrared Fluorescent Choline Kinase Inhibitors for Cancer Imaging and Therapy
Choline kinase alpha (ChoKa) deregulation is associated with a more aggressive phenotype and greater malignancy in many human cancers. Inhibitors of ChoKa induce apoptosis in tumorigenic cells, but validation of their specificity is difficult in vivo. Alterations in the profile of choline …
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Targeting bone-microenvironment-tumour cell interactions : IGF-1 receptor kinase inhibitors.
… showed that the novel IGF-1 receptor tyrosine kinase inhibitor PQIP significantly inhibited IGF-1 and breast cancer enhanced osteoclast formation. Western blot analysis suggested this may be due to the inhibition of both IGF-1 and cancer conditioned medium induced PI3k/Akt activation. Moreover, …
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Development of novel receptor tyrosine kinase inhibitors by a chemocentric approach
… fewer programs being run in the manner. The AXL kinase is a receptor tyrosine kinase (RTK) and a member of the TAM family, along with MER and TYRO3. AXL has long been associated with numerous types of cancer. Having been first discovered in 1991 in acute myeloid leukaemia (AML), it has gone on to …
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Role of Cyclin-Dependent Kinase Inhibitors in Estrogen Regulation of Adipogenesis
… has an effect on the levels of cell cycle inhibitors like p27 Kip1 (p27) and p21 Cip1 (p21) in breast cancer cell lines, estrogen might have an effect on the number of adipocytes by its effect on these proteins. Lack of p27 and p21 caused obesity due to hyperplasia in mice, which led to …
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Structure-Activity Relationship Studies of Sphingosine Kinase Inhibitors and Mitochondrial Uncouplers
… of sphingosine (Sph) by sphingosine kinase (SphK) and SphK exists as two isoforms-"SphK1 and SphK2, which differ with respect to their cellular activity and localization. As the key mediators in the synthesis of S1P, SphKs have attracted attention as viable targets for pharmaceutical …
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Use of Kinase Inhibitors to Illuminate Signaling Pathways in Breast Cancer
… factor 1 receptor (IGF-1R) and the protein kinase B (AKT) can also interfere and cause cell growth and replication. In this study, we propose that the use of a multi-agent treatment targeting the HER-2, IGF-1R, and AKT proteins will be more effective than a single-agent treatment of HER-2 …
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Design of Selective Plasmodium falciparum Kinase Inhibitors using Computer-Aided Drug Discovery
… campaign is based on the following Plasmodium kinases: Plasmodium falciparum phosphatidylinositol 4-kinase (PfPI4K) and Plasmodium falciparum cyclic guanosine monophosphate (cGMP)-dependent Protein Kinase (PfPKG). The aim of this study was to use computer-aided drug design (CADD) methods to …
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Design, Synthesis, and Structure-Activity Relationship Investigation of Selective Sphingosine Kinase Inhibitors
Sphingosine kinase 1 (SphK1) is the key enzyme catalyzing the formation of sphingosine-1-phosphate (S1P), which is an important signaling molecule that regulates multiple biological process including inflammatory responses. Elevated SphK1 activity as well as upregulated S1P levels is linked to …
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Structure-activity relationship studies and biological evaluation of selective sphingosine kinase inhibitors
… coupled receptors (S1P1-5). Sphingosine kinase (SphK) 1 and 2 phosphorylate sphingosine to S1P; these are the only enzymes known to mediate the phosphoryl transfer. Inhibiting either or both SphKs helps to modulate S1P, which may be useful as a therapeutic avenue for disease states where …
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Development of Rational Combination Therapy With Parp Inhibitors and Kinase Inhibitors In Tnbc
<p>Poly (ADP-ribose) polymerase inhibitors (PARPi) emerge as potential targeting drugs for BRCA-deficient cancers including triple negative breast cancer (TNBC). However, it has been reported that a subgroup of patients even with BRCA mutation fails to respond to PARPi in multiple clinical trials. …
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