DRUG

dapagliflozin

Type 2 diabetes (FDA 2014), heart failure (FDA 2020)

28 hypotheses across 7 therapeutic domains

CROSS-DOMAIN PATTERN

Same drug, multiple disease domains

dapagliflozin appears in hypotheses across 7 disease domains: ALS, Alzheimer, Epilepsy, Inflammatory bowel disease, Multiple sclerosis, Pancreatic cancer, Rheumatoid arthritis. Shared mediators that recur across at least two of those domains: SIRT1, AMPK.

Aggregated from the catalog. Biological interpretation of any multi-indication mechanism would require independent validation — this is a structural observation only.

ALL HYPOTHESES

Repurposing candidates for dapagliflozin

ALS 2

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	overexpression	0.248	Mid	reproduces known	none
AMPK	amyotrophic lateral sclerosis	0.248	Mid	novel signal	none

Alzheimer 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	tau acetylation	0.248	Mid	novel signal	none
SIRT1	Braak stage	0.248	Mid	novel signal	none
SIRT1	Aβ-induced neurotoxicity	0.248	Mid	novel signal	none
SIRT1	APP recycling	0.248	Mid	novel signal	none
SIRT1	APP transit to endosome	0.248	Mid	novel signal	none
SIRT1	tau accumulation	0.248	Mid	novel signal	none

Epilepsy 3

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	neuronal cell death	0.248	Mid	novel signal	none
AMPK	epileptiform network activity	0.248	Mid	novel signal	none
AMPK	spike-wave seizures	0.248	Mid	novel signal	none

Inflammatory bowel disease 3

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	radiation-induced inflammatory bowel disease	0.248	Mid	novel signal	none
AMPK	intestinal inflammation	0.248	Mid	partial evidence	none
AMPK	intestinal epithelial repair	0.248	Mid	novel signal	none

Multiple sclerosis 3

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	optokinetic response	0.248	Mid	novel signal	none
SIRT1	axon demyelination	0.248	Mid	novel signal	none
SIRT1	rheumatoid arthritis	0.248	Mid	partial evidence	none

Pancreatic cancer 10

Mediator	Outcome	Score	Tier	Lit. status	Trial
SGLT2	pancreatic adenocarcinoma	0.364	High	partial evidence	none
SGLT2	prostate adenocarcinoma	0.364	High	novel signal	none
SIRT1	proliferation	0.289	High	reproduces known	none
SIRT1	pancreatic cancer	0.289	High	partial evidence	completed
SIRT1	stemness marker expression	0.248	Mid	novel signal	none
SIRT1	patient survival	0.248	Mid	partial evidence	preclinical only
AMPK	invasion	0.248	Mid	novel signal	none
SIRT1	tumor-initiating capacity	0.248	Mid	novel signal	none
AMPK	pancreatic cancer progression	0.248	Mid	novel signal	none
AMPK	pancreatic ductal adenocarcinoma	0.248	Mid	partial evidence	none

Rheumatoid arthritis 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
SIRT1	TNF-alpha secretion	0.248	Mid	novel signal	none

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