A5023954887- Liver physiology and pathology
- Cancer Research and Treatments
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Enzyme Structure and Function
- Adenosine and Purinergic Signaling
- PI3K/AKT/mTOR signaling in cancer
- Cancer Treatment and Pharmacology
- Protein Structure and Dynamics
- Immune Cell Function and Interaction
- Cell Adhesion Molecules Research
- Virus-based gene therapy research
- Drug Transport and Resistance Mechanisms
- Lung Cancer Treatments and Mutations
- Pancreatic function and diabetes
- RNA and protein synthesis mechanisms
- Hepatocellular Carcinoma Treatment and Prognosis
- Muscle Physiology and Disorders
- Signaling Pathways in Disease
- RNA modifications and cancer
- Angiogenesis and VEGF in Cancer
Pfizer (United States)
1996-2023
National Cancer Institute
2016-2022
Center for Cancer Research
2022
National Institutes of Health
2008
General Atomics (United States)
1999
Scripps Research Institute
1999
Agouron Institute
1998
Weatherford College
1994
Cleveland Clinic
1994
California Institute for Biomedical Research
1993
Because of the critical roles aberrant signaling in cancer, both c-MET and ALK receptor tyrosine kinases are attractive oncology targets for therapeutic intervention. The cocrystal structure 3 (PHA-665752), bound to kinase domain, revealed a novel ATP site environment, which served as target guide parallel, multiattribute drug design. A 2-amino-5-aryl-3-benzyloxypyridine series was created more effectively make key interactions achieved with 3. In series, 2-aminopyridine core allowed...
The c-Met receptor tyrosine kinase and its ligand, hepatocyte growth factor (HGF), have been implicated in the progression of several human cancers are attractive therapeutic targets. PF-2341066 was identified as a potent, orally bioavailable, ATP-competitive small-molecule inhibitor catalytic activity kinase. selective for (and anaplastic lymphoma kinase) compared with panel >120 diverse serine-threonine kinases. potently inhibited phosphorylation c-Met-dependent proliferation, migration,...
A t(2;5) chromosomal translocation resulting in expression of an oncogenic kinase fusion protein known as nucleophosmin-anaplastic lymphoma (NPM-ALK) has been implicated the pathogenesis anaplastic large-cell (ALCL). PF-2341066 was recently identified a p.o. bioavailable, small-molecule inhibitor catalytic activity c-Met and NPM-ALK protein. also potently inhibited phosphorylation Karpas299 or SU-DHL-1 ALCL cells (mean IC(50) value, 24 nmol/L). In biochemical cellular screens, shown to be...
AAA ATPase conformational high jinks The protein p97 is an adenosine triphosphatase (ATPase) that uses energy from ATP hydrolysis to regulate substrates involved in intracellular quality control. Its role this central process makes it a target for cancer chemotherapy. Banerjee et al. used cryo-electron microscopy determine high-resolution structures multiple states of dynamic macromolecular machine. They also determined the structure ADP-bound state bound inhibitor. give insight into...
We have previously reported the isolation of a 35-kDa protein from A-431 cells that, in presence Ca2+, can serve as substrate for epidermal growth factor (EGF) receptor/tyrosine kinase (Fava, R.A., and Cohen, S. (1984) J. Biol. Chem. 259, 2636-2645). now report detection an antigenically related number, but not all, rat, pig, human tissues. These proteins also substrates EGF receptor/kinase Ca2+. All these share property reversible, Ca2+-dependent binding to particulate fraction (presumably...
NIH 3T3 cells were transfected with cDNA corresponding to human kidney prepro-epidermal growth factor (preproEGF) under control of the inducible mouse metallothionein promoter. The synthesis recombinant EGF precursor by these has provided us a model system for analysis structure and activity this precursor. In cells, was present as an intrinsic 170-kilodalton membrane protein well soluble in extracellular medium; both forms N glycosylated. Glycosylation determined (i) direct incorporation...
Vascular endothelial growth factor (VEGF) is a dimeric protein which induces formation of new blood vessels (angiogenesis) through binding to VEGF-receptor-2 tyrosine kinase (VEGFR2 TK) or KDR (kinase insert domain-containing receptor) on the surface cells. Angiogenesis has been shown be essential for malignancy tumors; therefore, VEGFR2 TK potential therapeutic target treatment cancer. Sequence homology studies indicate that contains three domains: extracellular (ligand-binding domain),...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCharacterization of translational-control ribonucleic acid isolated from embryonic chick muscleT. L. McCarthy, E. Siegel, B. Mroczkowski, and S. M. HeywoodCite this: Biochemistry 1983, 22, 4, 935–941Publication Date (Print):February 15, 1983Publication History Published online1 May 2002Published inissue 15 February 1983https://pubs.acs.org/doi/10.1021/bi00273a035https://doi.org/10.1021/bi00273a035research-articleACS PublicationsRequest reuse...
The upregulation of a limited number growth factors in our interferon-gamma transgenic model for regeneration within the pancreas lead us to propose that these are important during pancreatic regeneration. In this study, we have assessed influence two pancreas, epidermal factor (EGF) and keratinocyte (KGF), by ectopically expressing proteins under control human insulin promoter mice. This beta-cell-targeted expression either EGF or KGF resulted significant morphological changes, including...
Abstract Lipocortin I, a 35‐kDa protein, has been detected in terminally differentiated monocytes and neutrophils. This calcium‐phospholipid binding protein appears to be identical that can serve as substrate for the EGF‐receptor/tryosine kinase. We have used human myelocytic cell line HL‐60 explore whether differentiation of hematopoietic cells is associated with changes level lipocortin I. find toward macrophage lineage by addition phorbol esters or vitamin D 3 neutrophils dibutyryl cyclic...
Stable cell lines expressing the human epidermal growth factor (EGF) precursor have been prepared by transfection of mouse NIH 3T3 cells with a bovine papillomavirus-based vector in which kidney EGF cDNA has placed under control inducible metallothionein I promoter. Synthesis can be induced culturing 5 mM butyric acid or 100 microM ZnCl2. The synthesized these appears to membrane associated; none is detectable cytoplasm. size expressed approximately 150-180 kDa, larger than expected from its...
A biologically active form of the epidermal growth factor (EGF) precursor has been detected in human fluids and secretions. The secreted protein identified urine milk an apparent molecular mass 160-170 kilodaltons exhibits affinity for glycosaminoglycan heparin. More importantly, EGF is capable activating intrinsic tyrosyl kinase activity receptor. Our results demonstrate that soluble generated from membrane-anchored by a processing step takes place at cell surface involves truncation...
Baculovirus-mediated expression has become a powerful tool for the high yield production of functionally active recombinant proteins.In order to further enhance utility this system, we constructed versatile transfer vectors that facilitate secretion proteins from host insect cells by inserting functional secretory leader sequences downstream polyhedrin promoter.In-frame insertion cDNA results in synthesis fusion containing heterologous signal sequence which directs protein pathway.Human and...
Human p97 is a potential drug target in oncology. Mutation-driven resistance an obstacle to the long-term efficacy of targeted therapy. We found that ATPase activity for one CB-5083-resistant mutants was reduced, which also attenuated degradation K48 ubiquitinated proteins cells. To understand how mutant cells with significantly reduced can still grow, we discovered levels CHOP and NF-κB activation these cellular changes potentially protect HCT116 from death due lowered activity. In...
Abstract Pet dogs with naturally occurring cancers play an important role in studies of cancer biology and drug development. We assessed tolerability, efficacy, pharmacokinetic/pharmacodynamic relationships a first-in-class small molecule inhibitor valosin-containing protein (VCP/p97), CB-5339, administered to 24 tumor-bearing pet dogs. Tumor types included solid malignancies, lymphomas, multiple myeloma. Through stepwise dose schedule escalation schema, we determined the maximum tolerated...
Primary chick myoblast cultures demonstrate the ability to take up exogenously supplied polyadenylated RNA and express encoded information in a specific manner. This expression is shown exhibit tissue specificity. Analysis of creatine kinase activity monitored at various times incubation presence either or nonpolyadenylated indicates that only poly(A)+ mRNA capable being actively translated. Radioactively labled taken by cell time-dependent manner subsequently be associated with polysomes....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation and characterization of a bifunctionally spin-labeled mutant murine epidermal growth factor for saturation-transfer electron paramagnetic resonance studies the factor/receptor complexDennis L. Rousseau, Jr., Cheryl A. Guyer, Albert H. Beth, Ioannis Papayannopoulos, Baiyang Wang, Ray Wu, Barbara Mroczkowski, James V. StarosCite this: Biochemistry 1993, 32, 31, 7893–7903Publication Date (Print):August 1, 1993Publication History Published...