DRUG

Canagliflozin

Type 2 diabetes (FDA 2013)

30 hypotheses across 6 therapeutic domains

CROSS-DOMAIN PATTERN

Same drug, multiple disease domains

Canagliflozin appears in hypotheses across 6 disease domains: ALS, Epilepsy, Glioblastoma, Inflammatory bowel disease, Pancreatic cancer, Rheumatoid arthritis. Shared mediators that recur across at least two of those domains: HIF-1α, AMPK, mTOR, PD-L1.

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 Canagliflozin

ALS 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	amyotrophic lateral sclerosis	0.300	High	novel signal	none

Epilepsy 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	spike-wave seizures	0.300	High	novel signal	none
AMPK	epileptiform network activity	0.300	High	novel signal	none
mTOR	neuronal spiking activity	0.208	Mid	novel signal	none
HIF-1α	hippocampal neuron damage	0.208	Mid	novel signal	none
mTOR	mTOR-opathies	0.208	Mid	novel signal	none
HIF-1α	epilepsy	0.208	Mid	partial evidence	none

Glioblastoma 4

Mediator	Outcome	Score	Tier	Lit. status	Trial
mTOR	glioblastoma	0.277	High	partial evidence	none
PD-L1	overall survival	0.220	Mid	partial evidence	none
HIF-1α	glioma grade	0.208	Mid	novel signal	none
HIF-1α	temozolomide sensitivity	0.208	Mid	novel signal	none

Inflammatory bowel disease 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
AMPK	intestinal inflammation	0.300	High	partial evidence	none
AMPK	intestinal epithelial repair	0.300	High	novel signal	none
HIF-1α	ulcerative colitis	0.248	Mid	partial evidence	none
HIF-1α	inflammatory bowel disease	0.208	Mid	partial evidence	none
HIF-1α	disease activity	0.208	Mid	partial evidence	completed

Pancreatic cancer 13

Mediator	Outcome	Score	Tier	Lit. status	Trial
SGLT2	pancreatic adenocarcinoma	0.300	High	novel signal	none
AMPK	pancreatic ductal adenocarcinoma	0.300	High	partial evidence	none
AMPK	pancreatic cancer progression	0.300	High	partial evidence	none
AMPK	invasion	0.300	High	partial evidence	none
SGLT2	prostate adenocarcinoma	0.300	High	novel signal	none
PD-L1	type 2 autoimmune pancreatitis	0.220	Mid	novel signal	none
PD-L1	poor differentiation	0.220	Mid	novel signal	none
HIF-1α	tumor cell migration	0.208	Mid	novel signal	active
HIF-1α	cell invasion	0.208	Mid	novel signal	none
HIF-1α	radiation	0.208	Mid	novel signal	none
HIF-1α	pancreatic ductal adenocarcinoma	0.208	Mid	partial evidence	none
mTOR	pancreatic ductal adenocarcinoma	0.208	Mid	partial evidence	none
HIF-1α	poor prognosis	0.208	Mid	reproduces known	none

Rheumatoid arthritis 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
HIF-1α	rheumatoid arthritis	0.208	Mid	novel signal	none

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