THERAPEUTIC AGENT FOR TREATING HIF-1alpha-MEDIATED DISEASES BY INHIBITING AREL1 AND RESTORING PHD2 ACTIVITY
AssigneeBiochemgen Inc.
InventorDeug-Yong SHIN
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Abstract
Provided are agents and methods for treating or preventing diseases mediated by pathological HIF-1α activity. The disclosure provides an AREL1 inhibitor that restores PHD2 stability or activity and thereby decreases HIF-1α protein level and/or transcriptional activity. In exemplary embodiments, inhibition of AREL1 decreases expression of HIF-1α target genes such as VEGF and suppresses angiogenesis, supporting use of the disclosed agents for treating cancer and other angiogenesis-driven disorders. In some embodiments, the diseases include autoimmune and inflammatory diseases.
Claims24
A method of treating a HIF-1α-related disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an inhibitory nucleic acid that inhibits expression of apoptosis-resistant E3 ubiquitin protein ligase 1 (AREL1), thereby increasing a level or activity of prolyl hydroxylase domain-containing protein 2 (PHD2) and decreasing hypoxia-inducible factor-1 alpha (HIF-1α) activity in cells of the subject.
A method of treating a HIF-1α-related disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an agent that inhibits an interaction between AREL1 protein and PHD2 protein, thereby increasing PHD2 protein level and decreasing HIF-1α activity in cells of the subject.
A pharmaceutical composition comprising (i) an AREL1 inhibitor and (ii) a pharmaceutically acceptable carrier, wherein the AREL1 inhibitor is configured to increase PHD2 level or activity and decrease HIF-1α activity in a cell.
Dependencies are inferred from the claim text.