Table 1. Small molecule inhibitors of disordered states of proteins with proven in vivo efficacy.

Target	Disease family	Compound	Identification	In vivo efficacy	Clinical trials (Phase)	Structure	Ref.
ɑ-synuclein	Parkinson’s disease	Fasudil	Drug repurposing	Improved motor and cognitive functions at 10 and 30 mg/kg	Approved for use in humans but not assayed for Parkinson’s disease		[37]
Aβ	Alzheimer’s disease	SEN1576	Rational design	Reduced deficits in in vivo long-term potentiation and memory at 0.3 and 1 mg/kg	-		[38]
AR	Castration resistant prostate cancer	EPI-7170	Second generation lead compound from a phenotypic screen	Tumor growth inhibition at 25 mg/kg	NCT044212221 (1)		[39]
c-Myc	Cancer	MYCMI-6	Cell-based protein interaction screen	Apoptosis induction and reduction of tumor cell proliferation and microvascularity at 20 mg/kg	-		[40]
		EN4	Covalent ligand screen	Tumor growth inhibition at 50 mg/kg	-		[41]
EWS-FLI1	Ewing’s sarcoma	TK216	Rational design	Tumor growth inhibition at 100 mg/kg	NCT02657005 (1)		[42]
NUPR1	Pancreatic adenocarcinoma	ZZW-115	Ligand-based design	Tumor growth arrested at a 5 mg/kg	-		[43]
PTP1B	Diabetes, obesity	MSI-1436	Serendipity	Suppresses appetite, reduces body weight and improves plasma insulin at 5-10 mg/kg	Completed: NCT00806338 NCT00606112 NCT00509132 Discontinued: NCT02524951 (1)		[44, 45]
Tau	Alzheimer’s disease	TRx0237	In vitro aggregation assay	Reduces the brain atrophy rate at 4 mg/kg twice a day.	NCT03446001 (1)		[46, 47]

¹Clinical trial of EPI-7386 (structure not available).