A5036470968- Cancer Immunotherapy and Biomarkers
- Advanced Breast Cancer Therapies
- Multiple Myeloma Research and Treatments
- Fibroblast Growth Factor Research
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Kruppel-like factors research
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Monoclonal and Polyclonal Antibodies Research
- HIV/AIDS drug development and treatment
- Neurogenetic and Muscular Disorders Research
- RNA Research and Splicing
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- RNA modifications and cancer
- Congenital Anomalies and Fetal Surgery
- Orthopaedic implants and arthroplasty
- Chronic Lymphocytic Leukemia Research
- Infant Nutrition and Health
- Cancer, Hypoxia, and Metabolism
- Spine and Intervertebral Disc Pathology
- Chronic Myeloid Leukemia Treatments
- Pregnancy and preeclampsia studies
- Ubiquitin and proteasome pathways
- Eosinophilic Disorders and Syndromes
Incyte (United States)
2015-2024
Wilmington University
2017
University of Delaware
2007-2009
Einstein Medical Center Philadelphia
2007
Alfred I. duPont Hospital for Children
2005-2006
Alterations in fibroblast growth factor receptor (FGFR) genes have been identified as potential driver oncogenes. Pharmacological targeting of FGFRs may therefore provide therapeutic benefit to selected cancer patients, and proof-of-concept has established early clinical trials FGFR inhibitors. Here, we present the molecular structure preclinical characterization INCB054828 (pemigatinib), a novel, selective inhibitor 1, 2, 3, currently phase 2 trials. pharmacokinetics pharmacodynamics were...
Blocking the activity of programmed cell death protein 1 (PD-1) inhibitory receptor with therapeutic antibodies against either ligand (PD-L1) or PD-1 itself has proven to be an effective treatment modality for multiple cancers. Contrasting antibodies, small molecules could demonstrate increased tissue penetration, distinct pharmacology, and potentially enhanced antitumor activity. Here, we describe identification characterization INCB086550, a novel, oral, small-molecule PD-L1 inhibitor. In...
To determine whether ghrelin and cholecystokinin (CCK) are present in significant quantities term preterm human breast milk, to identify their source.Samples were collected from 10 mothers who delivered infants infants. Estimated fat content was measured. Ghrelin CCK levels measured whole skim milk samples using radioimmunoassays (RIA). Reverse transcriptase-polymerase chain reaction (RT-PCR) performed RNA mammary epithelial cells (hMECs) gland with primers specific ghrelin.The median level...
Mutations in calreticulin (mutCALR) are the second most common drivers of myeloproliferative neoplasms (MPNs) and yet, current therapeutic landscape lacks a selective agent for mutCALR-expressing MPNs. Here we show that monoclonal antibody INCA033989 selectively targets mutCALR-positive cells. antagonized mutCALR-driven signaling proliferation engineered cell lines primary CD34+ cells from patients with MPN. No binding or functional activity was observed lacking mutCALR. In mouse model MPN,...
Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes pathways; BET inhibitors have demonstrated activity in diverse models hematologic solid tumors. We report preclinical characterization INCB054329, a structurally distinct inhibitor that has been investigated phase I clinical trials.We used multiple myeloma to investigate vulnerabilities created by INCB054329 treatment could inform rational combinations.In addition c-MYC, decreased...
Abstract Bromodomains (BD) are protein modules that bind acetylated lysine residues and components of many epigenetic modifiers transcription factors. The BET (Bromodomain extra-terminal) family is composed four members each harboring two tandem BDs. proteins critical regulators through interactions with complexes including Mediator p-TEFb at gene promoter enhancer elements. Studies using genetic knockdown small molecule inhibitors have demonstrated targeting therapeutic in models cancer...
Abstract Aberrant signaling through Fibroblast Growth Factor Receptors (FGFR) has been reported in multiple types of human cancers. Genomic analyses squamous cell lung, gastric and urothelial tumors have revealed recurrent genetic alterations FGFR1, FGFR2 FGFR3 genes, respectively. FGFR proteins contribute to the development malignancies by promoting tumor proliferation, survival, migration supporting angiogenesis. Therefore targeting kinases may provide therapeutic benefit patients with...
Skeletal metastases are often complicated by progression to impending or pathologic fracture and fixation with polymethylmethacrylate (PMMA) bone cement is used for stabilization pain relief. Adjuvant therapy involving the delivery of PMMA composites mixed antibiotic chemotherapeutic agents requires an understanding rate drug diffusion from in addition measurement its mechanical properties pre- postelution drug. We have developed a method analysis drug-cement using PMMA/methotrexate as model...
Abstract Background Duchenne Muscular Dystrophy (DMD) is an X-linked genetic disorder that results in the production of a dysfunctional form protein, dystrophin. The mdx 5cv mouse model DMD which point mutation exon 10 dystrophin gene creates artificial splice site. As result, 53 base pair deletion occurs with coincident creation frameshift and premature stop codon. Using primary myoblasts from mice, single-stranded DNA oligonucleotides were designed to correct this mutation. Results...
Abstract Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with limited treatment options for advanced stage disease. Thus, there a critical medical need improved therapies. In approximately 10% HCC, focal amplicon at 11q13 harboring FGF19 has been reported. High levels have shown to drive HCC tumor development and progression in preclinical models, suggesting that selective targeting FGFR4, high affinity receptor FGF19, may be efficacious these tumors....
Abstract Aberrant signaling through Fibroblast Growth Factor Receptors (FGFR) has been reported in multiple types of human cancers. FGFR4 contributes to the development and progression subsets cancer: approximately 10 percent hepatocellular carcinoma (HCC), genetic amplification FGF19, encoding an endocrine FGF ligand that activates FGFR4-KLB receptors, reported. In models with this alteration, FGF19-FGFR4 is oncogenic antagonism axis shown be efficacious suggesting selective targeting may...
Supplementary Figure from Characterization of INCB086550: A Potent and Novel Small-Molecule PD-L1 Inhibitor
Abstract Activation of the Fibroblast Growth Factor (FGF)-FGF Receptor (FGFR) signaling axis occurs in many human cancers. In preclinical models, cell lines with genetic aberrations FGF/FGFR genes are preferentially inhibited by compounds that selectively target FGFR kinase. INCB54828 is a potent, selective, and reversible inhibitor FGFR1, 2 3 currently Phase clinical trials for advanced malignancies characterized FGF-FGFR alterations. this study, we investigated efficacy INCB054828 models...
Background Blocking the PD-L1 immune checkpoint axis with therapeutic antibodies against either ligand or PD-1 has proven to be an effective treatment modality for multiple cancer histologies. Small molecules targeting PD-L1/PD-1 represent alternate of blocking this pathway. INCB090244 is a small molecule that blocks interaction and restores T cell function similar clinical stage inhibitor INCB086550. Methods MDA-MB-231 CHO cells overexpressing were used investigate effects on dimerization,...
<p>Supplemental Tables 1 & 2 Supplemental Figure Legends Figures - 5</p>
<p>Supplemental Tables 1 & 2 Supplemental Figure Legends Figures - 5</p>
<div>AbstractPurpose:<p>Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes pathways; BET inhibitors have demonstrated activity in diverse models hematologic solid tumors. We report preclinical characterization INCB054329, a structurally distinct inhibitor that has been investigated phase I clinical trials.</p>Experimental Design:<p>We used multiple myeloma to investigate vulnerabilities created by INCB054329...
<div>AbstractPurpose:<p>Bromodomain and extraterminal domain (BET) proteins regulate the expression of many cancer-associated genes pathways; BET inhibitors have demonstrated activity in diverse models hematologic solid tumors. We report preclinical characterization INCB054329, a structurally distinct inhibitor that has been investigated phase I clinical trials.</p>Experimental Design:<p>We used multiple myeloma to investigate vulnerabilities created by INCB054329...
Abstract Background: Lung cancer is one of the most common tumors, accounting for approximately 1.8 million deaths worldwide in 2020. KRAS a frequently mutated oncogene, with mutations reported roughly 20-25% non-small cell lung cases. Specifically, at amino acid 12, resulting glycine to cysteine (G12C) substitution, occur 13% and 3% colon cancers, respectively, less other solid tumors. Recently, development covalent KRASG12C inhibitors has shown meaningful anticancer activity patients....
<div>Abstract<p>Blocking the activity of programmed cell death protein 1 (PD-1) inhibitory receptor with therapeutic antibodies against either ligand (PD-L1) or PD-1 itself has proven to be an effective treatment modality for multiple cancers. Contrasting antibodies, small molecules could demonstrate increased tissue penetration, distinct pharmacology, and potentially enhanced antitumor activity. Here, we describe identification characterization INCB086550, a novel, oral,...