Table 1.

Small-molecule compounds targeting the STAT3 SH2 domain.

Cpd	Protein-Based		Cell-Based			In Vivo Application Tested	Refs.
	Assay	IC50 or Ki [µM]	Cell Line	Readout	IC50 [µM]a
Stattic	pY binding	5.1	HepG2, MDA-MB-231	viability	3.8		[64,84,85]
			RAW264.7	pYSTAT3	s (20)	Osteoclasto genesis in C57/BL6 mice (10 mg/kg)
			M-SCC-17B, OSC-19, Cal33, UM-SCC-22	viability	2.2–3.5	Head and neck cancer xenograft (50 mg/kg)
STA-21			Caov-3	reporter assay	s (20)	Psoriatic disease in mouse model and phase I in clinical trial (NCT0104794)	[66,86]
			MDA-MB-435s, MDA-MB-468, MDA-MB-231	DNA binding, viability	s (20)
LLL-3			U373, MDA-MB-231	DNA binding	s (20)	Xenograft glioblastoma (50 mg/kg)	[68]
			MDA-MB-231	reporter assay	s (20)
LLL-12			MDA-MB-231, SK-BR-3, PANC-1, HPAC, U87, U373, A549	viability, pYSTAT3, reporter assay	0.16–3.09	Glioblastoma, breast cancer xenograft (2.5, 5 mg/kg) Lung cancer xenograft (20, 10 mg/kg)	[67,87]
S31-201		80	NIH 3T3/v-Src	DNA binding	86	Xenograft breast cancer (5 mg/kg)	[69,71]
			MDA-MB-468, MDA-MB-231	pYSTAT3	s (100)
			DU145, MDA468, OCI-AML-2	viability	28–112
SF-1-066	FP	20	NIH 3T3/v-Src	DNA binding	35		[69]
			DU145, MDA468, OCI-AML-2	viability	17–37
S31-1757	pY binding	13.5	HEK293	CoIP	s (50)		[88]
			MDA-MB-468, A549	pYSTAT3, reporter assay	s (50)
STX-0119			HeLa	reporter assay	74	Xenograft lymphoma (160 mg/kg)	[73]
			HEK293	FRET-based dimerization	s (50)
Cpd30-12	pY binding	114	HepG2, MEF/GFP-Stat3α, MDA-MB-468, MDA-MB-231, MBA-MD-435, MCF7	pYSTAT3, nuclear translocation, apoptosis	60		[72]
LY5	FP	2.5	U2OS, RH30, RD2, MDA-MB-231	viability, pYSTAT3	0.52–1.39	Xenograft breast cancer (5 mg/kg)	[79,89]
			UW426, UW288-1, DAOY	pYSTAT3	s (0.5)
Cpd9			HepG2/STAT3	reporter assay, pYSTAT3	3.57		[80]
			MDA-MB-468	viability	8.83
Cpd1	FP	~10	HeLa	reporter assay, DNA binding	~10		[81]

^a s (20): significant effect at 20 µM (or other concentration, as indicated); cpd—compound; FP—fluorescence polarization.