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Novel PIM 1 Kinase Inhibitor that Upregulates RUNX3 for the Treatment of Allergic Diseases

技術優勢

Investigators are currently testing a series of proprietary and novel PIM-1 kinase inhibitors in experimental models of asthma, allergic rhinitis and peanut-induced food allergy in mice.

技術應用

Treatment of allergic disease by upregulating or sustaining the expression of Runx3.

詳細技術說明

It is estimated that 50 million people in North America are affected by allergic conditions with an associated cost of more than $10 billion dollars yearly.The most common form of allergy, allergic rhinitis (nasal allergies), affects about 35 million Americans, 6 million of whom are children. The number of cases of asthma has doubled over the last 20 years affecting 15 million Americans, 5 million of whom are children. Even greater proportionate increases have been seen in atopic dermatitis and food allergy.Several antagonistic drugs are used to block the action of allergic mediators, or to prevent activation of cells and degranulation processes. These include antihistamines, glucocorticoids, epinephrine (adrenaline), and theophylline. Anti-leukotrienes, such as Montelukast (Singulair) or Zafirlukast (Accolate), are FDA approved for treatment of allergic diseases. Anti-cholinergics, decongestants, mast cell stabilizers, and other compounds thought to impair eosinophil chemotaxis, are also commonly used. Although these drugs help to alleviate the symptoms of allergy, to some extent, but they play a limited role in chronic treatment of allergic disorders.Runt-related transcription factors (Runx) are a novel family of transcription factors which are key regulators of lineage-specific gene expression. The data suggest that Runx3 plays a critical role in regulating T-cell development, the differentiation of Th1/Th2 cells and Th1/Th2 cytokine production, and the development of an allergic disease.

*Abstract

Dr. GelfandΓÇÖs laboratory at National Jewish Health has shown that the proto-oncogene serine/threonine-protein kinase (PIM-1) increases upon allergen sensitization and is responsible for the downregulation of Runx3. Further, they have shown in mouse models of allergy that the upregulation of Runx3 can be achieved by inhibiting PIM-1 kinase. This strategy substantially reduced allergic responses in mice.Therefore, upregulating Runx3 by targeting PIM-1 kinase represents a novel approach for treating allergic diseases. Scientists at National Jewish Health and the University of Colorado have also developed novel PIM-1 kinase inhibitors because existing ones suffer from a lack of specificity and problems associated with distribution, metabolism and excretion.

*Principal Investigation

Name: Erwin Gelfand, Chairman

Department: Department of Pediatrics

附加資料

Inventor: Ostrov, David A. | Law, Brian K. | Corsino, Patrick
Priority Number: US8569356B2
IPC Current: A01N004318 | A01N003302 | A01N004306 | A61K0031135 | A61K003138 | C07C021100 | C07D033308 | C07D033504 | C07D033506 | C07D049500
US Class: 514432 | 514438 | 514646 | 514657 | 549023 | 549080 | 564429 | 564441
Assignee Applicant: University of Florida Research Foundation Inc.inesville
Title: Cyclin dependent kinase inhibitors
Usefulness: Cyclin dependent kinase inhibitors
Summary: For the treatment of a subject (such as mammals, rodents, sheep, dog, cow, chickens, amphibians, or reptiles) suffering from or susceptible to a cell proliferative disorder, e.g. cancer such as acute leukemia, chronic leukemia, breast cancer, or prostate cancer.
Novelty: Treatment of subject, e.g. mammals, suffering from or susceptible to cell proliferative disorder, e.g. cancer, by administering cyclin-dependent kinase down-regulator compound

主要類別

診斷/治療

細分類別

癌症/腫瘤

國家/地區

美國