Compounds and salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof and uses thereof are described. In certain aspects and embodiments, the described compounds or salts thereof, formulations thereof, conjugates thereof, derivatives thereof, forms thereof are active on at least one Raf protein kinase. In certain aspects and embodiments, the described compounds are active in inhibiting proliferation of a Ras mutant cell line. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of B-Raf V600E mutant protein kinase, including melanoma, glioma, glioblastoma multiforme, pilocytic astrocytoma, colorectal cancer, thyroid cancer, lung cancer, ovarian cancer, prostate cancer, liver cancer, gallbladder cancer, gastrointestinal stromal tumors, biliary tract cancer, and cholangiocarcinoma. Also described are methods of use thereof to treat diseases and conditions, including diseases and conditions associated with activity of c-Raf-1 protein kinase, including acute pain, chronic pain or polycystic kidney disease.

Compounds and methods for kinase modulation, and indications therefor

MAP kinase kinase kinase kinases (MAP4Ks) belong to the mammalian Ste20-like family of serine/threonine kinases. MAP4Ks including MAP4K1/HPK1, MAP4K2/GCK, MAP4K3/GLK, MAP4K4/HGK, MAP4K5/KHS, and MAP4K6/MINK have been reported to induce JNK activation through activating the MAP3K-MAP2K cascade. The physiological roles of MAP4Ks in immunity and inflammation are largely unknown until recent studies using biochemical approaches and knockout mice. Surprisingly, JNK is not the major target of MAP4Ks in immune cells; MAP4Ks regulate immune responses through novel targets. HPK1 inhibits T-cell receptor (TCR) signaling and B-cell receptor signaling via inducing phosphorylation/ubiquitination of SLP-76 and BLNK, respectively. GLK activates TCR signaling through phosphorylating/activating PKCθ. T-cell-mediated immune responses and Th17-mediated experimental autoimmune diseases are enhanced in HPK1 knockout mice but ameliorated in GLK knockout mice. Consistently, HPK1 levels are decreased in peripheral blood mononuclear cells and T cells from patients with psoriatic arthritis and systemic lupus erythematosus (SLE), respectively. Moreover, GLK levels are increased in T cells from patients with SLE, rheumatoid arthritis, or adult-onset Still's disease; the percentages of GLK-overexpression T cells are correlated with the disease activity. In addition, HGK phosphorylates and induces TRAF2 protein degradation, leading to negative regulation of IL-6 production in resting T cells. Loss of HGK in T cells results in spontaneous systemic inflammation and type 2 diabetes in mice. HGK is also involved in cancer cell migration. To date, the phenotypes of knockout mice for GCK, KHS, and MINK have not been reported; the roles of these three MAP4Ks in immune cell signaling are discussed in this review. Taken together, MAP4K family kinases play diverse roles in immune cell signaling, immune responses, and inflammation.

MAP4K Family Kinases in Immunity and Inflammation.

Compounds active on Ret are described, as well as methods of using such compounds. Also described are crystal structures of Ret surrogates that were determined using X-ray crystallography. The use of such Ret surrogate crystals and strucural information can, for example, be used for identifying molecular scaffolds and for developing ligands that bind to and modulate Ret and for identifying improved ligands based on known ligands.

Compounds and methods for development of Ret modulators

The present invention relates to novel sequences for use in detection, diagnosis and treatment of cancers, especially lymphomas. The invention provides cancer-associated (CA) polynucleotide sequences whose expression is associated with cancer. The present invention provides CA polypeptides associated with cancer that are present on the cell surface and present novel therapeutic targets against cancer. The present invention further provides diagnostic compositions and methods for the detection of cancer. The present invention provides monoclonal and polyclonal antibodies specific for the CA polypeptides. The present invention also provides diagnostic tools and therapeutic compositions and methods for screening, prevention and treatment of cancer.

Therapeutic targets in cancer

Compounds active on the receptor protein tyrosine kinases c-kit and/or c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or conditions and/or c-fms-mediated diseases or conditions, and methods for the use thereof.

Compounds modulating c-fms and/or c-kit activity and uses therefor

A method of identifying a compound that induces apoptosis is disclosed The method includes identifying compounds that inhibit the expression and/or activity of a target Also disclosed are methods for inducing apoptosis by inhibiting one of the targets The invention further includes methods for the diagnosis of a tumor that include determining the level of at least one of the targets as a biomarker in a patient sample, the level of the biomarker being indicative of the presence of tumor cells

Targets for controlling cellular growth and for diagnostic methods

Methods for identifying nucleic acid molecules and polypeptides that participate in angiogenesis and tumorigenesis, and associated methods and products are provided.

Compositions and methods relating to angiogenesis and tumorigenesis

Since the early stages of tumorigenesis involve adhesion, escape from immune surveillance, vascularization and angiogenesis, we devised a strategy to study the expression profiles of all publicly known and putative secreted and cell surface genes. We designed a custom oligonucleotide microarray containing probes for 3531 secreted and cell surface genes to study 5 diverse human transformed cell lines and their derivative xenograft tumors. The origins of these human cell lines were lung (A549), breast (MDA MB-231), colon (HCT-116), ovarian (SK-OV-3) and prostate (PC3) carcinomas. Three different analyses were performed: (1) A PCA-based linear discriminant analysis identified a 54 gene profile characteristic of all tumors, (2) Application of MANOVA (Pcorr < .05) to tumor data revealed a larger set of 149 differentially expressed genes. (3) After MANOVA was performed on data from individual tumors, a comparison of differential genes amongst all tumor types revealed 12 common differential genes. Seven of the 12 genes were identified by all three analytical methods. These included late angiogenic, morphogenic and extracellular matrix genes such as ANGPTL4, COL1A1, GP2, GPR57, LAMB3, PCDHB9 and PTGER3. The differential expression of ANGPTL4 and COL1A1 and other genes was confirmed by quantitative PCR. Overall, a comparison of the three analyses revealed an expression pattern indicative of late angiogenic processes. These results show that a xenograft model using multiple cell lines of diverse tissue origin can identify common tumorigenic cell surface or secreted molecules that may be important biomarker and therapeutic discoveries.

/pdf/expression-analysis-of-secreted-and-cell-surface-genes-of-16w45xzxiu.pdf

Expression analysis of secreted and cell surface genes of five transformed human cell lines and derivative xenograft tumors

A method of identifying a compound that induces apoptosis in a cell is dosclosed. The method includes contacting the cell with a putative apoptosis-inducing compound and determining whether the compound inhibits a target selected from the group consisting of APLP2, ENSA, FBN2, FIBL-6, PRNP, STRN4, XPR1, SLC5A6, SLC31A1, GFER, and PCTK1. Also disclosed are methods for inducing apoptosis in a cell by inhibiting one of the targets. The invention further includes methods for the diagnosis of a tumor that include determining the level of one of the targets as a marker in a patient sample, the level of the marker being indicative of the presence of tumor cells.

Cellular gene targets for controlling cell growth

L'invention concerne une methode d'identification d'un compose qui induit l'apoptose dans une cellule. Cette methode consiste a mettre en contact la cellule avec un compose induisant l'apoptose putatif et a determiner si le compose inhibe une cible selectionnee parmi un groupe comprenant APLP2, ENSA, FBN2, FIBL-6, PRNP, STRN4, XPR1, SLC5A6, SLC31A1, GFER, et PCTK1. Ladite invention a egalement trait a des methodes d'induction de l'apoptose dans une cellule par inhibition d'une des cibles, ainsi qu'a des methodes de diagnostic d'une tumeur consistant a determiner le niveau d'une des cibles en fonction d'un marqueur dans un echantillon d'un patient, le niveau du marqueur indiquant la presence de cellules tumorales.

Cibles geniques cellulaires pour la regulation de la croissance cellulaire

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Robert Stull

Author Tools

Chat about Author