A5075742013- Lung Cancer Treatments and Mutations
- Radiopharmaceutical Chemistry and Applications
- RNA modifications and cancer
- HER2/EGFR in Cancer Research
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Cancer therapeutics and mechanisms
- Cancer Immunotherapy and Biomarkers
- Monoclonal and Polyclonal Antibodies Research
- Click Chemistry and Applications
- Colorectal Cancer Treatments and Studies
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Medical Imaging Techniques and Applications
- Cancer-related molecular mechanisms research
- Cytokine Signaling Pathways and Interactions
- Chronic Lymphocytic Leukemia Research
- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Phagocytosis and Immune Regulation
- interferon and immune responses
- Immune Cell Function and Interaction
- ATP Synthase and ATPases Research
- PI3K/AKT/mTOR signaling in cancer
Moderna Therapeutics (United States)
2018-2023
Clovis Oncology (United States)
2013-2014
Cancer Genetics (United States)
2013
Vanderbilt University
2013
Science Applications International Corporation (United States)
2013
National Cancer Institute
2013
Tris Pharma (United States)
2008
AMAG Pharmaceuticals (United States)
2007
Population Council
2000
University Hospitals of Cleveland
1976
Patients with non-small cell lung cancer (NSCLC) activating EGF receptor (EGFR) mutations initially respond to first-generation reversible EGFR tyrosine kinase inhibitors. However, clinical efficacy is limited by acquired resistance, frequently driven the EGFR(T790M) mutation. CO-1686 a novel, irreversible, and orally delivered inhibitor that specifically targets mutant forms of EGFR, including T790M, while exhibiting minimal activity toward wild-type (WT) receptor. Oral administration as...
Local mRNA therapy encoding inflammatory cytokines and T cell costimulator OX40L mediates persistent anticancer immunity across tumor models.
Targeted therapies that suppress B cell receptor (BCR) signaling have emerged as promising agents in autoimmune disease and malignancies. Bruton's tyrosine kinase (Btk) plays a crucial role development activation through the BCR pathway represents new target for diseases characterized by inappropriate activity. <i>N</i>-(3-(5-fluoro-2-(4-(2-methoxyethoxy)phenylamino)pyrimidin-4-ylamino)phenyl)acrylamide (CC-292) is highly selective, covalent Btk inhibitor sensitive quantitative assay...
While immune checkpoint inhibitors such as anti-PD-L1 are rapidly becoming the standard of care in treatment many cancers, only a subset treated patients have long-term responses. IL12 promotes antitumor immunity mouse models; however, systemic recombinant had significant toxicity and limited efficacy early clinical trials.We therefore designed novel intratumoral mRNA therapy to promote local tumor production while mitigating effects.A single dose (m)IL12 induced IFNγ CD8+ T-cell-dependent...
PI3Kα has been identified as an oncogene in human tumors. By use of rational drug design, a targeted covalent inhibitor 3 (CNX-1351) was created that potently and specifically inhibits PI3Kα. We demonstrate, using mass spectrometry X-ray crystallography, the selective covalently modifies on cysteine 862 (C862), amino acid unique to α isoform, PI3Kβ, -γ, -δ are not modified. is able (EC(50) < 100 nM) inhibit signaling PI3Kα-dependent cancer cell lines, this leads potent antiproliferative...
Patients with non-small cell lung carcinoma (NSCLC) activating mutations in epidermal growth factor receptor (EGFR) initially respond well to the EGFR inhibitors erlotinib and gefitinib. However, all patients relapse because of emergence drug-resistant mutations, T790M accounting for approximately 60% resistance. Second-generation irreversible are effective against vitro, but retain affinity wild-type (EGFR(WT)). These have not provided compelling clinical benefit T790M-positive patients,...
Changes in mRNA expression for estrogen receptor (ERβ) relation to mRNAs LH (LHr) and cytochrome P450 enzymes were examined granulosa theca cells from proestrous rat ovarian follicles. Of the 30 ovaries harvested 15 adult rats, 24 processed situ hybridization, remaining used reverse transcription-polymerase chain reaction. Messenger RNAs ERβ, LHr, side-chain cleavage enzyme (P450scc), 17α-hydroxylase (P450c17), aromatase (P450arom), steroidogenic acute regulatory protein (StAR) localized...
Abstract Objective To determine the disease‐modifying activity and mechanism of action orally available methionine aminopeptidase type 2 inhibitor, [(1R)‐1‐carbamoyl‐2‐methyl‐propyl]‐carbamic acid‐(3R,4S,5S,6R)‐5‐methoxy‐4‐[(2R,3R)‐2‐methyl‐3‐(3‐methyl‐but‐2‐enyl)‐oxiranyl]‐1‐oxa‐spiro [2.5] oct‐6‐yl ester (PPI‐2458), in a rat model peptidoglycan–polysaccharide (PG‐PS)–induced arthritis. Methods Arthritis was induced rats by administration PG‐PS, causing tarsal joint swelling histopathologic...
Fumagillin and related compounds have potent antiproliferative activity through inhibition of methionine aminopeptidase-2 (MetAP-2). It has recently been reported that MetAP-2 is highly expressed in germinal center B cells center-derived non-Hodgkin's lymphomas (NHL), suggesting an important role for proliferating cells. Therefore, we determined the importance normal transformed by evaluating effects on form function centers NHL cells.To examine PPI-2458 morphology, spleen sections from...
Over the past few decades, melanoma has shown fastest growing incidence rate of all cancers. This malignancy is clinically defined by its potential to rapidly metastasize, and advanced metastatic melanomas are highly resistant existing therapeutic regimens. Here, we report that PPI-2458, a novel, orally active agent fumagillin class irreversible methionine aminopeptidase-2 (MetAP-2) inhibitors, potently inhibited proliferation B16F10 cells in vitro, with growth inhibitory concentration 50%...
A test for the lymphokine eosinophil stimulation promoter (ESP) has been adapted to study of Trichinella spiralis infections in mice and used as an aid diagnosis trichinosis a patient. With use soluble antigen extracted from T. larvae peritoneal exudate cells rich eosinophils obtained with four weeks' duration, dose-response curve was constructed analyzed. The larval antigens greatly enhanced migration but had no effect on schistosomiasis, nor did schistosome egg have any trichinosis. On two...
Abstract Introduction: Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond well to tyrosine kinase inhibitors. However, clinical efficacy is limited by the development of resistance. The most common mechanism resistance a second site mutation within exon 20 (T790M), observed in ∼50% cases. Our goal was develop mutant-selective inhibitor that potently inhibits as T790M while sparing wild-type for treatment NSCLC patients. Such drug has potential...
The present investigations of the recently discovered lymphokine eosinophil stimulation promoter have (1) shown that assay system is highly sensitive and reproducible via establishment dose-response curves their statistical analysis, (2) demonstrated direct specific with use eosinophilrich peritoneal exudate cells obtained from mice either schistosomiasis or trichinosis, (3) indirect test splenic lymphocytes both above method radioisotope-labeled antigens, (4) provided information on roles...
Abstract Introduction: Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond well to the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, clinical efficacy is limited by development of resistance. The most common mechanism resistance a second site mutation within exon 20 (T790M), observed in ∼50% cases. CO-1686 an irreversible inhibitor that targets mutant forms inhibiting (L858R, delE746-A750) gatekeeper (T790M) but not wild-type...
ABSTRACT: The enzyme 5α‐reductase plays a significant role in the prostate to amplify action of testosterone (T) by converting it more potent androgen, dihydrotestosterone (DHT). feedback inhibition gonadotropin secretion from pituitary has not been elucidated. Therefore, we investigated on T vitro and vivo models. Castration reported increase activity glands. Hence, effect castration duration conversion DHT homoge‐nates responsiveness monolayer cell cultures gonadotropin‐releasing hormone...
<p>Table S1</p>
<p>Supplementary Methods</p>
<p>Supplementary Figures S1-S11</p>
<p>Supplementary Methods</p>