Table 1.

Validated PC inhibitors.

Molecules	Type	In vivo validated uses	Hits by	Selectivity indexa (nM)
TPRARRRKKRT-NH2 (80)	Peptidic	Protects against Pseudomonas exotoxin and anthrax infection Synergism with antibiotics	Extension of the Furin cleaving sequence in the HA of avian influenza A H5N1	23	furinb
				162	PACE4
				441	PC4
				232	PC5/6
				152	PC7
8-Amino-octanoyl-RARRRKKRT-NH2 (81)	Tailed peptide	Protect from anthrax infection in vivo Synergism with antibiotics	Derivation of TPRARRRKKRT peptide with lipid complexion to provide cellular entry	8	furin
				3	PC5/6
				430	PC7
				3	PACE4
Hexa-D-arginine (82, 83)	Peptidic	Prevents and treats PEA sepsis in mice	PS-SPCLS	265	furin
				106
				13 000	PC1b
				1875	PC7
				206	PC5/6
				580	PACE4
Nona-D-arginine peptide (82, 84, 85)	Peptidic	Reduces considerably the corneal damages of the keratitis caused by Pseudomonas aeruginosa and prophylaxis uses	Levoratory modification of the nona-L-arginine version previously identified by PS-SPCLs of L- and D-hexapeptides	1	furinb
				19	PC5/6
				81	PC7
CMGTINTRTKKC (86)	Peptidic	Limits rhabdomyosarcoma tumors progression Synergism with antineoplasic agent	Screening for phage-displayed peptides binding to rhabdomysarcoma cells	N/A	N/A
Decanoyl-RVKR-CMK (45, 87–89)	CMK-peptide	Reduces considerably squamous cell carcinomas (~30%) in TPA induced epidermal proliferation	Coupling CMK group used to study other proteinases on Arg and Lys peptidic sequences	1	furin
				0.12	PC5/6
				0.12	PC7
				3.6	PACE4
Aminopyrrolidineamide (19, 90, 91)	Small molecule	Downregulates (~70% reduction) mice liver HMG-CoA reductase and fatty acid synthase and decrease cholesterol synthesis. Also, in vitro arenavirus’ glycoprotein processing reduction	High-throughput screening	170	SKI-1/S1P
				No significant inhibition for furin, trypsin, elastase, Xia factor, thrombin, kallikrein

^aBased on K_i values against recombinant PC (human if not mentioned) and values marked with (^b) give emphasis to the selectivity.