TABLE 3.

Limitations of potential PIN1 inhibitors.

Drug	Covalent or non-covalent	Details	Tested cancer types	Limitations
Juglone	Covalent	Irreversible inhibits PIN1 PPIase activity Inhibits cell proliferation and xenograft tumor growth	HCC Prostate cancer	Non-specific inhibition of RNA polymerase II and Rab4
PiB	Non-covalent	Inhibits PIN1 PPIase activity and cell proliferation	Colon cancer	No testing in animal model
Dipentamethylene thiuram monosulfide (DTM)	Non-covalent	Inhibits PIN1 PPIase activity and cell proliferation	Colon cancer	No testing in animal model
TME-001	Non-covalent	Inhibits PIN1 PPIase activity and cell proliferation	Cervical cancer	No testing in animal model
5′-nitro-indirubinoxime (5′-NIO)	N.A.	Reduce PIN1 protein expression Inhibits cell proliferation	Lung cancer	No testing in animal model
KPT-6566	Covalent	Induce PIN1 protein degradation Inhibits cell proliferation More specific PIN1-inhibitory activity	Breast cancer Prostate cancer Lung cancer Pancreatic cancer	No testing in clinical trial

HCC, Hepatocellular carcinoma; N.A., Not applicable.