. 2019 Sep 24;9:933. doi: 10.3389/fonc.2019.00933

Table 2.

Anti-cancer activities of small-molecule membrane-permeant specific inhibitors of Kv1.3 channels.

Name of the inhibitor and the value of EC₅₀	Cancer cell lines affected	Mechanisms of anti-cancer activity	Maximal percentage of eliminated cancer cells	References
5-(4-phenylobutoxy)- psoralen (Psora-4) EC₅₀ = 3 nM	Jurkat T, human neoplastic B-CLL cells, SAOS-2, B16F10, CTLL-2-Kv1.3	Inhibition of cell proliferation combined with an induction of the mitochondrial pathway of apoptosis in cancer cells sparing normal ones.	Approximately 80% at 50 μM concentration when co-applied with inhibitors of membrane multidrug resistance transporters (MRP).	(41–43)
5-(4-phenoxybutoxy) psoralen (PAP-1) EC₅₀ = 2 nM	Jurkat T, human neoplastic B-CLL cells, SAOS-2, B16F10, CTLL-2-Kv1.3	As mentioned above.	Approximately 80% at 50 μM concentration when co-applied with inhibitors of membrane multidrug resistance transporters (MRP).	(41–43)
N,5-bis (4-chloro phenyl)-3-(1-methyl ethylimino)-5H-phenazin-2-amine (clofazimine) EC₅₀ = 300 nM	Jurkat T, human neoplastic B-CLL cells, SAOS-2, B16F10, As PC-1, Capan-1, Panc-1, Mia PaCa 2, Bx PC-3, Colo357, GL261, A172, LN308.	As mentioned above. Statistically significant negative correlation between cancer cells' survival and the expression of Kv1.3 channels	Approximately 90% at 50 μM concentration, reduction of tumor size of induced melanoma by 90% after 6 days of treatment, reduction of tumor weight of induced pancreatic ductal adenocarcinoma (PDAC) by more than 50% after 20 days of treatment.	(29, 41–46)
Triphenylphosphonium PAP-1 derivative -PAPTPEC₅₀ = 31 nM	human neoplastic B-CLL cells, B16F10, As PC-1, Capan-1, Panc-1, Mia PaCa 2, Bx PC-3, Colo357, GL261, A172, LN308.	Induction of the mitochondrial pathway of apoptosis in cancer cells sparing normal ones.	More than 90% at 10 μM concentration, reduction of tumor size of induced melanoma by 80% after 16 days of treatment, reduction of tumor weight of induced pancreatic ductal adenocarcinoma (PDAC) by more than 50 % after 20 days of treatment.	(44–46)
Triphenylphosphonium PAP-1 derivative -PCARBTPEC₅₀ = 6.5 nM for the product of hydrolysis - PAPOH	Jurkat T, human neoplastic B-CLL cells, SAOS-2, B16F10, As PC-1, Capan-1, Panc-1, Mia PaCa 2, Bx PC-3, Colo357, GL261, A172, LN308.	As mentioned above.	More than 90% at 10 μM concentration, reduction of tumor size of induced melanoma by 80% after 16 days of treatment, reduction of tumor weight of induced pancreatic ductal adenocarcinoma (PDAC) by more than 60 % after 20 days of treatment.	(44–46)
Triphenylphosphonium PAP-1 derivative -PCTPEC₅₀ = 6.5 nM for the product of hydrolysis—PAPOH	Jurkat T, CTLL-2-Kv1.3, As PC-1, Capan-1, Panc-1, Bx PC-3.	As mentioned above.	More than 90% at 20 μM concentration when co-applied with inhibitors of membrane multidrug resistance transporters (MRP).	(47)