Methods for using and biomarkers for ampk-activating compounds
AssigneeRigel Pharmaceuticals, Inc.
InventorsYasumichi Hitoshi, Yonchu Jenkins, Vadim Markovtsov, Todd Kinsella, Tian-Qiang Sun
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Abstract
Disclosed are methods of using AMPK-activating compounds, for example, in the treatment of cancer and disorders of vascular flow. Also disclosed are biomarkers for AMPK and uses thereof, for example, in the diagnosis and treatment of AMPK-linked disorders. In certain embodiments, the AMPK-activating compounds have the structural formula wherein E, J, T, D1, D2, D3, the ring system denoted by “B”, T, R3, R4, w and x are as described herein.
Claims48
A method of treating cancer, increasing vascular flow, treating a disorder of vascular flow, treating a disorder of glycogen storage, treating pulmonary arterial hypertension, treating vasculitis or treating venous ulcers, in a subject in need thereof, the method comprising administering to the subject a therapeutically-effective amount of an AMPK-activating compound or a pharmaceutically acceptable salt, prodrug or N-oxide thereof, or a solvate or hydrate thereof.
A method of sensitizing a cancer cell to apoptosis, upregulating p53 activity in a cancer cell, inducing a cytotoxic effect in a cancer cell, or down-regulating UHRF1 (Np95) in a cell, the method comprising contacting the cancer cells with an effective amount of an AMPK-activating compound or a pharmaceutically acceptable salt, prodrug or N-oxide thereof, or a solvate or hydrate thereof.
A method of determining the degree of AMPK activation in a subject comprising:
- optionally, administering to the subject an AMPK-activating compound;
- then
- obtaining a sample from the subject;
- and
- measuring the concentration of a biomarker of AMPK activation in the sample from the subject.
Dependencies are inferred from the claim text.