Table 2.

Cathepsin D inhibitors in chronological order.

Inhibitor	Mechanism	Ref.
Natural Compounds
Pepstatin A from Actinomycetes	Non-competitive inhibitor	[141]
Cycloheximide from Streptomyces griseus	Protein synthesis inhibitor	[142]
The 22-kDa cathepsin D inhibitor protein of potatoes (PDI) from Solanum tuberosum	Reversible inhibitor	[143]
Equistatin from Actinia equina	Reversible inhibitor	[144]
Fucoidan from brown seaweeds and algae	Down-regulator of the expression	[126]
Oxymatrine from Sophora flavescens	Down-regulator of the expression	[125]
Morin hydrate from Maclura pomifera, Maclura tinctoria, Psidium guajava	Reversible inhibitor	[127]
Synthetic compounds
Dithiophosgene	Irreversible covalent inhibitor	[145]
2,2-Dichloro-1,3-dithiacyclobutanone
Diazo compounds	Irreversible covalent inhibitor	[146]
Pro-Pro-Phe-Phe-Val-D-Leu	Reversible inhibitor	[147]
Cbz-Val-Val-(3S4S)-statine	Reversible inhibitor	[148]
Ibu-His-Pro-Phe-HCys-Sta-Leu-NH-[CH2]2-S-Acm	Reversible inhibitor	[149]
Derivatives of 4-(morpholinylsulphonyl)-L-Phe-P2-(cyclohexyl)Ala psi[isostere]-P1′-P2′	Irreversible covalent inhibitor	[150]
Lentiviral shRNA constructs	RNA interference inhibitor	[76]
Acylguanidines	Reversible inhibitor	[131,132]
LY2811376	Reversible inhibitor	[128]
PtdIns(3)P 1 RNA aptamer	Inhibitor of PtdIns(3)P	[136]
Macrocyclic inhibitors	Competitive inhibitor	[36]
Necrostatin-1	Suppressor of activity	[130]
Polytherapy
RL2 2, with chloroquine, Ku55933, and rapamycin from Streptomyces hygroscopicus	Suppressor of activity	[134]
Praeruptorin C from Peucedanum praeruptorum and U0126	Inhibitor through ERK1/2 3 signaling pathway	[133]

¹ phospatidylinositol 3-phosphate; ² recombinant analog of human milk protein lactaptin; ³ extracellular signal-regulated kinase 1/2.