PDIA4 inhibitors and use thereof for inhibiting β-cell pathogenesis and treating diabetes
AssigneeAcademia Sinica
InventorsWen-Chin Yang, Keng-Chang Tsai
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Abstract
Disulfide-Isomerase A4 (PDIA4) inhibitors and use thereof for inhibiting pancreatic β-cell pathogenesis and treating diabetes are disclosed. Drug candidates that inhibit PDIA4 with IC50 values ranging from 4 μM to 300 nM are identified. The compounds are highly active in augmenting insulin secretion from pancreatic β-cells. The representative compound No. 8 (4,5-dimethoxy-2-propiolamidobenzoic acid), alone or in combination with metformin, is effective in preserving pancreatic β-cell function, treating and/or reversing, returning blood glucose concentration to a normal level in a diabetic.
Claims18
A protein disulfide-isomerase A4 (PDIA4) inhibitor or a PDIA4 inhibitor anti-diabetic drug or an insulin-secretion augmenting agent which is a PDIA4 inhibitor, being selected from the group consisting of:
- and pharmaceutically acceptable salts thereof.
A PDIA4 inhibitor-containing pharmaceutical composition, comprising:
- (i) a PDIA4 inhibitor selected from the group consisting of:
- and pharmaceutically acceptable salts thereof;
- and
- (ii) a pharmaceutically acceptable carrier or excipient.
The PDIA4 inhibitor-containing pharmaceutical composition of 5, wherein the PDIA4 inhibitor is selected from
- 8 or a pharmaceutically acceptable salt thereof.
A PDIA4 inhibitor-containing pharmaceutical composition, comprising:
- (i) a PDIA4 inhibitor selected from the group consisting of:
- and pharmaceutically acceptable salts thereof, and
- (ii) metformin.
Dependencies are inferred from the claim text.