A5072113438- T-cell and Retrovirus Studies
- Chronic Myeloid Leukemia Treatments
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Chronic Lymphocytic Leukemia Research
- Monoclonal and Polyclonal Antibodies Research
- PI3K/AKT/mTOR signaling in cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Eosinophilic Disorders and Syndromes
- Synthesis and biological activity
- Quinazolinone synthesis and applications
- Protein Kinase Regulation and GTPase Signaling
- Click Chemistry and Applications
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Protein Tyrosine Phosphatases
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- Transgenic Plants and Applications
- Insect Resistance and Genetics
- T-cell and B-cell Immunology
- Cancer therapeutics and mechanisms
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Virus-based gene therapy research
Torrey Pines Institute For Molecular Studies
2003
Columbia University
2001
Athenex (United States)
2000
Tonix Pharmaceuticals (United States)
2000
Novartis (China)
2000
Novartis (Switzerland)
1990-1998
Brigham and Women's Hospital
1997
Harvard University
1997
Oregon Health & Science University
1997
Blood Cancer UK
1997
BCR-ABL is a constitutively activated tyrosine kinase that causes chronic myeloid leukemia (CML). Since activity essential to the transforming function of BCR-ABL, an inhibitor could be effective treatment for CML.
STI571 (formerly known as CGP 57148B) is a protein-tyrosine kinase inhibitor that currently in clinical trials for the treatment of chronic myelogenous leukemia. selectively inhibits Abl and platelet-derived growth factor (PDGF) receptor tyrosine kinases vitro blocks cellular proliferation tumor Bcr-abl- or v-abl-expressing cells. We have further investigated profile against related kinases. was found to potently inhibit activity alpha- beta-PDGF receptors stem cell factor, but not closely...
The platelet-derived growth factor (PDGF) receptor is a member of the transmembrane protein family with intrinsic protein-tyrosine kinase activity. We describe potent inhibitor (CGP 53716) that shows selectivity for PDGF in vitro and cell. compound inhibition PDGF-mediated events such as autophosphorylation, cellular tyrosine phosphorylation, c-fos mRNA induction response to stimulation intact cells. In contrast, ligand-induced autophosphorylation epidermal (EGF) receptor, insulin...
Following ligand binding, the epidermal growth factor receptor (EGF-R) autophosphorylates itself on tyrosine residues located in its carboxyl terminus; vitro, three sites are highly phosphorylated, while two other phosphorylated to lesser extents. In presence of Src protein-tyrosine kinase, vitro phosphorylation minor autophosphorylation was increased, and four additional were phosphorylated. EGF stimulation, (Tyr-891 Tyr-920) found be a colorectal cell line (DLD-1) breast tumor (MCF7). The...
In the course of random screening a pool CIBA chemicals, two pyrazolopyrimidines 1 and 2 have been identified as fairly potent inhibitors EGF-R tyrosine kinase. Using pharmacophore model for ATP-competitive interacting with active site protein kinase (PTK), class pyrazolo[3,4-d]pyrimidines was then optimized in an interactive process leading to series 4-(phenylamino)-1H-pyrazolo[3,4-d]-pyrimidines highly The most compounds 13, 14, 15, 17, 19, 22, 26, 28, 30 this inhibited PTK IC50 values...
Using a pharmacophore model for ATP-competitive inhibitors interacting with the active site of EGF-R protein tyrosine kinase (PTK), 4-(phenylamino)-7H-pyrrolo[2,3-d]pyrimidines have been identified as novel class potent inhibitors. In an interactive process, this compounds was then optimized. 13, 14, 28, 36, 37, and 44, most series, inhibited PTK IC50 values in low nanomolar range. High selectivity toward panel nonreceptor kinases (c-Src, v-Abl) serine/threonine (PKC α, PKA) observed....
Deregulated signal transduction via the epidermal growth factor receptor (EGF-R) family of protein-tyrosine kinase receptors is associated with proliferative diseases. We describe a class compounds (4,5-dianilinophthalimides) that inhibit EGF-R in vitro high selectivity. In cells, 4,5-dianilinophthalmide selectively inhibited both ligand-induced and p185c-erbB2 autophosphorylation c-fos mRNA induction. Antitumor activity could be demonstrated vivo against xenografts A431 SK-OV-3 tumors,...
Various derivatives of thiazolidine-diones have been identified as tyrosine protein kinase inhibitors. The epidermal growth factor (EGF) receptor and c-src were inhibited in vitro with IC50 values the range 1-7 microM. v-abl was not by thiazolidine-diones. Inhibition found to be specific for kinases. serine/threonine kinases observed. active shown inhibit EGF-induced autophosphorylation, either or intact cells, also EGF-dependent BALB/MK A431 cell lines (IC50 1-3 microM). Growth...
The Src family of kinases are held in an inactive state by interaction their SH2 domain with a C-terminal phosphotyrosine. Dephosphorylation this site can reactivate Src; however, recent evidence suggests that activation also occur without dephosphorylation. In study, platelet-derived growth factor receptor phosphorylation on Tyr-213 specifically blocked binding its to phosphopeptide corresponding the regulatory sequence, while other sequences, such as or peptide from epidermal receptor, was...
Phenylamino-pyrimidines represent a novel class of inhibitors the protein kinase C with high degree selectivity versus other serine/threonine and tyrosine kinases. Steady state kinetic analysis N-(3-[1-imidazolyl]-phenyl-4-(3-pyridyl)-2-pyrimidinamine (5), which showed potent inhibitory activity, revealed competitive kinetics relative to ATP. The adjacent H-bond acceptor pyrimidine moiety next an donor phenylamine was found be crucial for activity....
[(Alkylamino)methyl]acrylophenones and (alkylamino)propiophenones, bearing a spacer moiety such as the benzyloxy or (benzoylsulfonyl)oxy group in 4-position, represent novel class of inhibitors epidermal growth factor (EGF) receptor protein tyrosine kinase with high degree selectivity versus other serine/threonine kinases. The most active compounds inhibited EGF from A431 cell membranes IC50 values < 0.5 microM. Derivatives substituent 4-position aromatic ring both proliferation an...
Abstract Expression of rat protein kinase C‐δ (PKC‐δ ) and PKC‐ξ in insect cells using recombinant baculovirus resulted the production proteins with a molecular size approximately 76 kD 78 kD, respectively, as determined by immunoblotting subtype‐specific antisera. Although cDNA encoded for 592 amino acids, was also generated vitro transcription/translation. Extracts expressing PKC‐δ were able to bind phorbol ester levels comparable extracts PKC‐α. No binding was, however, detected cell...