Table 1.

Overview of potential S100 inhibitors.

Inhibitor	S100 Target	Mechanism of Action	Current Status	References
Small Molecule Inhibitors
Calcimycin	Transcription of S100A4	Inhibition of β-catenin expression, which inhibits Wnt/β-catenin signalling and therefore expression of S100A4	Pre-clinical	[214]
Sulindac	Transcription of S100A4	Inhibition of β-catenin expression, which inhibits Wnt/β-catenin signalling and therefore expression of S100A4	Pre-clinical	[215]
Niclosamide	Transcription of S100A4	Inhibition of β-catenin/TCF complex binding to the S100A4 promoter leading to reduced expression of S100A4	Phase II for treatment of CRC metastasised patients	[216,217]
Trifluoperazine (TFP)	S100A4	Ca2+-S100A4/TFP dimers form a pentameric ring, disabling interaction between S100A4 and myosinIIA	Pre-clinical	[218,219]
Tasqinimod	S100A9	Binds S100A9 and blocks interaction with RAGE and TLR4	Phase III completed for treatment of metastatic castration-resistant prostate cancer (mCRPC)	[220,221,222,223]
1,2,4-triazoles	S100A10	Competes with annexin A2 for the binding to S100A10	Pre-clinical	[224,225]
Pentamidine	S100B	Binds to S100B and inhibits interaction with p53, therefore restoring p53 activity	Phase II for treatment of refractory melanoma	[226,227,228]
Cromolyn 5-methyl cromolyn	S100P	Binds to S100P and prevents interaction with RAGE	Pre-clinical	[229,230,231]
Antibodies
6B12	S100A4	Binds extracellular S100A4 and thereby acts as an immunomodulating agent	Pre-clinical	[232,233]
5C3	S100A4	Binds to and neutralises S100A4	Pre-clinical	[234]
6F5	S100A7	Binds to S100A7 and thereby blocks S100A7/RAGE interaction	Pre-clinical	[235]
Ab45	S100A8/S100A9	Binds extracellular S100A8/S100A9 heterodimer and therefore reduces metastasis	Pre-clinical	[236]
2H8	S100P	Binds S100P and therefore reduces tumour growth and metastasis	Pre-clinical	[237]
miRNA
miR-187-3p	S100A4	S100A4 silencing results in reduced metastasis and EMT in HCC	Pre-clinical	[238]
miR-149-3p	S100A4	S100A4 silencing results in inhibition of invasion and migration in bladder cancer cells	Pre-clinical	[239]
miR-193a	S100A6	S100A6 silencing results in suppression of proliferation, invasion, migration, and angiogenesis within lung cancer models	Pre-clinical	[240]
miR-26b-5p	S100A7	S100A7 silencing inhibits proliferation, invasion, and migration of intrahepatic cholangiocarcinoma cells	Pre-clinical	[241]
miR-24	S100A8	S100A8 silencing leads to decreased proliferation and invasion of laryngeal carcinoma cells and increases sensitivity of endometrial carcinoma cells for paclitaxel	Pre-clinical	[242,243]
miR-6884-5p	S100A16	S100A16 silencing reduces proliferation, invasion, and EMT in gastric cancer	Pre-clinical	[244]