Table 3.

Summary of key KLK3 inhibitors reported in the literature.

Type	Relevance	Agent	Description/pharmacological data/therapeutic impact
β-lactam analogs	Unclear	2-azetidinone	IC50 = 226 nM [122]
	Prostate cancer	Benzoxazinone derivatives	Ki = 300 nM. 30 times more selective compared to chymotrypsin (Ki = 8.5 μM) [126]
		Triazole derivatives	Ki = 500 nM. 10 times more selective compared to chymotrypsin (Ki = 5.4 μM) [126]
Cysteine and serine protease inhibitors	Prostate cancer	Azapeptides	Ki = 500 nM [125]
Heavy metal cations	Semen liquefaction	Zn2+	Inhibits KLK3 activity at 10 mM [8]
			IC50 = 20 μM [41]
		Hg2+	Inhibits KLK3 activity at 10 mM [8]
			IC50 = 150 μM [41]
		Cu2+	IC50 = 150 μM
		Cd2+	IC50 = 200 μM
		Co2+	IC50 = 500 μM
Heavy metal chelator	Semen liquefaction	1,10-phenanthroline	Inhibits KLK3 activity at 50 mM [8]
Pan-serine protease inhibitors	Semen liquefaction	PMSF	Inhibits KLK3 activity at 5 mM [8]
		AEBSF	Inhibits KLK3 activity at 5 mM [8]
	Prostate cancer	PMSF	Inhibits KLK3 activity at 20 mM [115]
		AEBSF	Inhibits KLK3 activity at 10 mM [115]
Peptide aldehyde inhibitor	Prostate cancer	Z-SSKLL-H	Ki = 6.5 μM [128]
Peptidyl boronic acid inhibitor	Prostate cancer	Z-SSKL(boro)L	Ki = 65 nM. 60 times more selective compared to chymotrypsin (Ki = 3.9 μM). Reduction in free and total KLK3 serum levels in human prostate cancer xenografts produced in nude mice upon intravenous administration of 33 mg/kg dose for two cycles of three consecutive days/5 days [128]
		Z-SSKn(boro)L	Ki = 48.4 nM. Norleucine substitution of Z-SSKL(boro)L [129]
		Ahx-FSQn(boro)Bpg	Ki = 72 nM. Eight times more selective compared to chymotrypsin (Ki = 580 nM). Reduction in free and total KLK3 serum levels in human prostate cancer xenografts produced in nude mice upon intravenous administration of 10 mg/kg dose for three cycles of five consecutive days/week [130]
RNA aptamer	Prostate cancer	Not applicable	Synthetic RNA molecules (92 mer) selected from pools of random-sequence oligonucleotides to specifically bind active KLK3 [131]