DRUG

tofacitinib

Rheumatoid arthritis (FDA 2012), ulcerative colitis (FDA 2018)

31 hypotheses across 9 therapeutic domains

CROSS-DOMAIN PATTERN

Same drug, multiple disease domains

tofacitinib appears in hypotheses across 9 disease domains: ALS, Alzheimer, Depression, Epilepsy, Glioblastoma, Inflammatory bowel disease, Multiple sclerosis, Pancreatic cancer, Type 2 diabetes. Shared mediators that recur across at least two of those domains: STAT3, IFN-γ, JAK/STAT pathway.

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 tofacitinib

ALS 2

Mediator	Outcome	Score	Tier	Lit. status	Trial
STAT3	muscle atrophy	0.208	Mid	partial evidence	none
IFN-γ	ALS	0.208	Mid	partial evidence	preclinical only

Alzheimer 3

Mediator	Outcome	Score	Tier	Lit. status	Trial
JAK-STAT pathway	Alzheimer's disease	0.333	High	reproduces known	completed
STAT3	Alzheimer's disease	0.208	Mid	reproduces known	completed
STAT3	cognitive deficits	0.208	Mid	partial evidence	preclinical only

Depression 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
IL-8	major depressive disorder	0.230	Mid	partial evidence	none

Epilepsy 5

Mediator	Outcome	Score	Tier	Lit. status	Trial
IFN-γ	ketogenic diet adaptation	0.208	Mid	novel signal	none
STAT3	persistence of reactive glial states	0.208	Mid	novel signal	none
STAT3	general cell loss	0.208	Mid	novel signal	none
STAT3	imprinting of epileptic activity patterns	0.208	Mid	novel signal	none
STAT3	GABAergic neuron loss	0.208	Mid	novel signal	none

Glioblastoma 3

Mediator	Outcome	Score	Tier	Lit. status	Trial
JAK/STAT pathway	anti-inflammatory environment	0.277	High	partial evidence	none
STAT3	glioblastoma progression	0.208	Mid	novel signal	none
IFN-γ	ferroptosis	0.208	Mid	novel signal	none

Inflammatory bowel disease 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
JAK/STAT pathway	post-operative recurrence	0.277	High	novel signal	none
STAT3	DSS-induced colitis	0.208	Mid	reproduces known	none
IFN-γ	fibrosis	0.208	Mid	reproduces known	preclinical only
IFN-γ	recurrence	0.208	Mid	reproduces known	active
STAT3	UC	0.208	Mid	reproduces known	active
IFN-γ	surgical relapse	0.208	Mid	novel signal	none

Multiple sclerosis 4

Mediator	Outcome	Score	Tier	Lit. status	Trial
IFN-γ	experimental autoimmune encephalomyelitis	0.208	Mid	partial evidence	none
IFN-γ	relapse rate	0.208	Mid	reproduces known	none
IFN-γ	oral microbiome dysbiosis	0.208	Mid	novel signal	none
IFN-γ	NMOSD	0.208	Mid	novel signal	none

Pancreatic cancer 6

Mediator	Outcome	Score	Tier	Lit. status	Trial
JAK2	poor prognosis	0.230	Mid	reproduces known	none
STAT3	pancreatic ductal adenocarcinoma	0.208	Mid	novel signal	none
IFN signaling	pancreatic ductal adenocarcinoma	0.208	Mid	novel signal	none
STAT3	immune escape	0.208	Mid	novel signal	none
STAT3	pancreatic cancer	0.208	Mid	partial evidence	completed
STAT3	drug resistance	0.208	Mid	partial evidence	completed

Type 2 diabetes 1

Mediator	Outcome	Score	Tier	Lit. status	Trial
C-reactive protein	type 2 diabetes	0.230	Mid	reproduces known	none

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