Table 1.

PRL inhibitors.

Inhibitor	Potency and selectivity	Discovery	Cellular efficacy	Reference
Pentamidine	Similar activity against PRL-1/2/3: IC₅₀ < 0.277 μg/ml using peptide substrate; also shows activity against other phosphatases.	The clue comes from that pentamidine has similar anti-leishmania action as SSG, which has anti-cancer activity via inhibiting PTPs.	Inhibits growth of five human cancer cell lines with PRL expression within the concentration ranges 0.3-5 μg/ml; inhibits growth of WM9 human melanoma tumors in nude mice and results in tumor necrosis.	(Pathak et al., 2002)
Thienopyridone	PRL-1: IC₅₀ = 173 nM PRL-2: IC₅₀ = 277 nM PRL-3: IC₅₀ = 128 nM Shows selectivity over 11 other PTPs using DiFMUP substrate.	High-throughput screening of the Roche chemical library to search for molecules that inhibits PRL phosphatase activity using peptide substrate.	Induce p130Cas cleavage and apoptosis in Hela and RKO cells; inhibits anchorage-independent growth in RKO and HT-29 cells; inhibits HUVEC cells migration but not proliferation.	(Daouti et al., 2008)
Iminothienopyridinedione 13 (JMS-053)	PRL-1: IC₅₀ = 50 nM PRL-2: IC₅₀ = 53 nM PRL-3: IC₅₀ = 18 nM Minimal effect on 25 other phosphatases at 1 μM using DiFMUP substrate.	Identified during the process of SAR study of thienopyridone to increase its stability and reduce its potential toxicity.	Inhibit migration, spheroid growth and RhoA activity in human ovarian cancer cells; reduce growth of drug-resistant ovarian cancer in a murine xenograft model.	(McQueeney et al., 2018; Salamoun et al., 2016)
Rhodanine and its derivatives	Inhibit human PRL-3 activity with IC₅₀ range 0.9-9.5 μM; compound 5e is the most active one with IC₅₀ 0.9 μM against PRL-3; not tested on other PRLs and PTPs (DiFMUP).	Rhodanine skeleton was identified by high throughput screening of chemical library of Korean Chemical Bank and 14 derivatives were synthesized for SAR study.	Compound 5e reduces invasiveness of B16F10 cells in vitro.	(Ahn et al., 2006)
CG-707 and BR-1	Inhibit human PRL-3 activity: CG-707: IC₅₀ = 0.8 μM BR-1: IC₅₀ = 1.1 μM Minimal effects on 9 other PTPs (DiFMUP). Suppress cancer cell migration: CG-707: IC₅₀ = 5 μM BR-1: IC₅₀ = 7 μM	Using cell-based assay to screen rhodanine derivatives.	Inhibit the migration and invasion of cancers that express PRL-3 without affecting proliferation; change the expression of EMT markers.	(Min et al., 2013)
Analog 3	Inhibit human PRL-3 activity PRL-3: IC₅₀ = 31 μM. Shows acceptable selectivity against PTP1B, TCPTP and VHR and no selectivity against PRL-1 and PRL-2 (DiFMUP).	Ligand based virtual screening of Zinc database combined with SAR study and biochemical screening.	Specifically inhibits migration of cells that express PRLs in a dose-dependent manner and does not affects proliferation of HEK cells at 50 μM.	(Hoeger et al., 2014)
Compound-43 and several analogs.	Not phosphatase inhibitors, Trimerization disruptors 30 mg/kg cmpd-43 inhibits melanoma xenograft tumor growth; ~2 μM cmpd-43 suppress 50% MeWo cells survival	Sequential structure-based virtual screening of compounds of Asinex and ChemBridge subsets in the ZINC database.	Specifically inhibit cell proliferation and migration of PRL-1 overexpressing cells; suppress MeWo cells proliferation and migration, inhibit melanoma xenograft tumor growth.	(Bai et al., 2016)
Curcumin	Inhibit human PRL-3 activity PRL-3: IC₅₀ = 31 μM Shows acceptable selectivity against PTP1B, TCPTP and VHR and no selectivity against PRL-1 and PRL-2	Extracted from spice turmeric, has been known to be able to induce apoptosis of cancer cells and suppress cell migration and angiogenesis.	Inhibits mRNA expression of PRL-3 and partial PRL-2; specifically inhibits adhesion and migration of cancer cells with high PRL-3 expression; inhibits growth and metastasis of xenograft tumors in mice.	(L. Wang et al., 2009)
Ginkgetin and sciadopitysin	Inhibited PRL-3 activity: gfinkgetin: IC₅₀ = 50 μM sciadopitysin: IC₅₀ = 25.8 μM Not tested on other PTPs and PRLs	Bioflavonoids identified in the MeOH extract of the young branches of Taxus cuspidata	Reduce invasiveness of B16F10 cells in vitro	(Choi et al., 2006)
Natural anthraquinone compounds: compound 1 and 2	Inhibited PRL-3 activity: Compound 1: IC₅₀ = 5.2 μg/ml Compound 2: IC₅₀ = 1.3 μg/ml. Not tested on other PRLs and PTPs.	Extracted from the roots of Rubia akane.	Compound 2 was shown to inhibit migration of DLD-1 cells but not proliferation.	(Moon et al., 2010)
PRL-1 and PRL-3 mAb (mouse); Chimeric mouse and human PRL-3 mAb; PRL-3-zumab	High selectivity: PRL-1 and PRL-3 mAb only prevents metastatic tumor formation of cells that express respective PRL. PRL-3-zumab is more potent than 5-FU, a first-line chemotherapeutic drug for gastric cancer.	Generated using hybridoma technology and their specificity was confirmed.	Efficiently and specifically block metastatic tumors formation of cells overexpressing PRL; also inhibit tumor formation of cancer cells expressing endogenous PRL; prevents recurrence of PRL-3 positive tumors after surgery.	(Guo et al., 2012; Ke Guo et al., 2008; Thura et al., 2016