A5053527900- Computational Drug Discovery Methods
- Enzyme function and inhibition
- Ureteral procedures and complications
- PARP inhibition in cancer therapy
- Cell death mechanisms and regulation
- Receptor Mechanisms and Signaling
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Advanced Biosensing Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
- Phosphodiesterase function and regulation
- Lung Cancer Treatments and Mutations
- Cell Image Analysis Techniques
- Amino Acid Enzymes and Metabolism
- Kidney Stones and Urolithiasis Treatments
- Chemical Reactions and Isotopes
- Renal and Vascular Pathologies
- Neuroendocrine Tumor Research Advances
- Melanoma and MAPK Pathways
- Retinoids in leukemia and cellular processes
- Synthesis and Catalytic Reactions
- Macrophage Migration Inhibitory Factor
- Effects of Radiation Exposure
- RNA modifications and cancer
- Medicinal Plants and Neuroprotection
Purdue University West Lafayette
2016-2025
University of Illinois Urbana-Champaign
2003-2015
Purdue University System
2015
Johnson & Johnson (United States)
2013-2014
Urbana University
2007
University of Minnesota
2006
Indiana University – Purdue University Fort Wayne
2004
Although chimeric antigen receptor (CAR) T cell therapies have demonstrated considerable success in treating hematologic malignancies, they simultaneously been plagued by a cytokine release syndrome (CRS) that can harm or even kill the cancer patient. We describe CAR strategy which activation and killing be sensitively regulated adjusting dose of low molecular weight adapter must bridge between to initiate tumor eradication. By controlling concentration dosing schedule administration, we...
Apoptosis is generally believed to be a process that requires several hours, in contrast non-programmed forms of cell death can occur minutes. Our findings challenge the time-consuming nature apoptosis as we describe discovery and characterization small molecule, named Raptinal, which initiates intrinsic pathway caspase-dependent within minutes multiple lines. Comparison mechanistically diverse panel apoptotic stimuli reveals Raptinal-induced proceeds with unparalleled speed. The rapid...
// Jiayin Shen 1 , Karson S. Putt 2 Daniel W. Visscher 3 Linda Murphy 4 Cynthia Cohen 5 Sunil Singhal 6 George Sandusky 7 Yang Feng 8 Dimiter Dimitrov and Philip Low 1,2 Department of Chemistry, Purdue University, West Lafayette, IN, USA Center for Drug Discovery, Laboratory Medicine Pathology, Mayo Clinic, Rochester, MN, Biochemistry Molecular Biology, Clinic College Medicine, Pathology Emory University Hospital, Atlanta, GA, Division Thoracic Surgery, Hospital the Pennsylvania School...
A number of folate receptor (FR) targeted small molecular drugs and monoclonal antibodies have been introduced into clinical trials to treat FR positive cancers. Because the therapeutic efficacy these depends prominently on level FR-α expression cancer cells, patients commonly selected for FR-targeted therapies based intensity a folate-targeted radioimaging agent. Unfortunately, uptake such imaging agents can be mediated by both major isoforms receptor, FR-β. Logically, if cell population in...
Late-stage malignant melanoma is a cancer that refractory to current chemotherapeutic treatments. The average survival time for patients with such diagnosis 6 months. In general, the vast majority of anticancer drugs operate through induction cell cycle arrest and death in either DNA synthesis (S) or mitosis (M) phase cycle. Unfortunately, same mechanisms melanocytes possess protect cells from damage often confer resistance derive their toxicity S M arrest. Described herein combinatorial...
Folate-receptor-positive activated macrophages are critical for the development and maintenance of many chronic inflammatory autoimmune diseases. Previously, small-molecule folate-targeted conjugates were found to specifically bind these in vitro selectively accumulate at sites inflammation vivo. While have shown promise, use a folate-targeted, higher cargo capacity nanovehicle may prove superior delivering imaging or therapeutic agents This nanoparticle strategy has been demonstrated...
Although CAR T cell therapies have proven to be effective in treating hematopoietic cancers, their abilities regress solid tumors been less encouraging. Mechanisms explain these disparities focused primarily on differences cancer heterogeneity, barriers penetration of tumors, and immunosuppressive microenvironments. To evaluate the contributions tumor-associated macrophages (TAMs) myeloid-derived suppressor cells (MDSCs) efficacies, we exploited ability a folate-targeted Toll-like receptor 7...
Estrogen receptor alpha (ERalpha) plays an important role in several human cancers. Most current ERalpha antagonists bind the ligand binding pocket and compete for with estrogenic ligands. Instead of traditional approach targeting estrogen to ER, we describe a strategy using high throughput fluorescence anisotropy microplate assay identify small molecule inhibitors consensus response element (cERE) DNA. We identified fluorescein-labeled (fl)cERE evaluated their specificity, potency,...
Proof-of-principle studies in ovarian, lung, and brain cancer patients have shown that fluorescence-guided surgery can enable removal of otherwise undetectable malignant lesions, decrease the number cancer-positive margins, permit identification disease-containing lymph nodes would normally evaded resection. Unfortunately, current arsenal tumor-targeted fluorescent dyes does not all cancers, raising need to design new tumor-specific illuminate currently cancers. In an effort a more universal...
// Jyoti Roy 1, 2 , Karson S. Putt 1 Domenico Coppola 3 Marino E. Leon Farah K. Khalil Barbara A. Centeno Noel Clark 4 Valerie Stark 5 David L. Morse Philip Low Center for Drug Discovery, Purdue University, West Lafayette IN 47907 USA Department of Chemistry, Anatomic Pathology, H. Lee Moffitt Cancer Center, Tampa FL 33612 Tissue Core, Imaging and Metabolism, Technology Excellence, Correspondence to: Low, e-mail: plow@purdue.edu Keywords: cholecystokinin receptor, CCK2R, CCKBR, gastrin...
The selective induction of death in cancer cells is a major challenge modern medicine. In this communication we describe the synthesis an 88-membered combinatorial library, and subsequent evaluation these compounds for their ability to selectively induce apoptosis cancerous cells. A compound was identified from library that induces U-937 HL-60 cell lines. This remarkably pro-apoptotic agent lines, as it does not significant noncancerous white blood cells, even at concentrations high 1000 μM.
Aim: We endeavored to create a folate-targeted liposome (Fol-liposome) that could selectively target areas of inflammation. Materials & methods: Fol-liposomes were prepared with encapsulated DiD fluorophore or betamethasone (BM) image and treat an adjuvant-induced rat model rheumatoid arthritis. Results: accumulated in arthritic paws greater extent than nontargeted liposomes. When these used encapsulate BM administered rats, animals exhibited less paw swelling, lower arthritis scores,...
Most therapies for autoimmune and inflammatory diseases either neutralize or suppress production of cytokines produced by activated macrophages (e.g., TNFα, IL-1, IL-6, IL-17, GM-CSF). However, no approved directly target this subset macrophages.First, we undertook to examine whether the folate receptor beta (FR-β) positive subpopulation macrophages, which marks in animal models rheumatoid arthritis, might constitute prominent population inflamed lesions humans. Next, utilized anti-FR-β...
As the delivery of selectively targeted cytotoxic agents via antibodies or small molecule ligands to malignancies has begun show promise in clinic, need identify and validate additional cellular targets for specific therapeutic is critical. Although a multitude cancers have been using folate receptor, PSMA, bombesin somatostatin LHRH, αvβ3, there notable lack ligand/receptor pairs found within GI tract. Because selective tract expression cholecystokinin 2 receptor (CCK2R), we undertook...
To egress from its erythrocyte host, the malaria parasite, Plasmodium falciparum, must destabilize membrane by activating an tyrosine kinase. Because imatinib inhibits kinases and because has a good safety profile, we elected to determine whether coadministration of with standard care (SOC) might be both well tolerated therapeutically efficacious in patients. Patients uncomplicated P. falciparum region Vietnam where one third patients experience delayed parasite clearance (DPC; continued...
Peracetic acid is gaining usage in numerous industries who have found a myriad of uses for its antimicrobial activity. However, rapid high throughput quantitation methods peracetic and hydrogen peroxide are lacking. Herein, we describe the development high-throughput microtiter plate based assay upon well known trusted titration chemical reactions. The adaptation these chemistries to absorbance sequential determination specifically total amount peroxides present solution described. results...
As tumors grow, vasculature is often deficient or malformed, resulting in many localized areas of hypoxia. Cells located these hypoxic regions exhibit an altered gene expression pattern that can significantly alter resistance to conventional anticancer treatments such as ionizing radiation and chemotherapeutic drugs. A priori knowledge the level hypoxia within a tumor may better guide clinical care. In effort create specific imaging agent, ligand for tissue marker, carbonic anhydrase IX (CA...
As general cytotoxins are still the backbone of anticancer chemotherapy, identification selective inducers cell death in defined cancer types and subtypes is one major goals modern oncology research. Thus, compounds identified with such selectivity have utility as probes cancer-type-specific biological pathways, optimized versions potential targeted therapy. Described herein discovery that compound 13-D selectively induces apoptotic white blood lines but not other lines. Further experiments...