Table 1.

Summary of the diseases due to enzyme misfolding for which a non-inhibitor pharmacological chaperone has been described.

	Protein	Second Generation Pharmacological Chaperone			Reference
		Name	Structure	Known Binding Site (Identification Mode)
Gaucher disease (OMIM# 231000)	Gcase	2-(2-((4-bromophenyl)amino)-2-oxoethoxy)-N-(2-(methyl(phenyl)amino)-2-oxoethyl)benzamide (ML266 or NCGC00182186)		No	[49]
		2-[2-[(4-iodophenyl)amino]-2-oxoethoxy]-N-[2- (methylphenylamino)-2-oxoethyl]-benzamide (NCGC607)		No	[50,51]
		N-(4-ethynylphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxamide (ML198 or NCGC00188758)		No	[49,52,53]
		5,7-dimethyl-N-((1r,4r)-4-(pentyloxy)cyclohexyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (LTI-291)		No	[55,56]
		((S)-N-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)-N-methyl-2-(pyridin-3-yl)quinazolin-4-amine (S-181)		Yes (co-crystallization with a derivatives)	[63,64,65]
Fabry disease (OMIM# 301500)	α-Gal A	2,6-dithiopurine (DTP)		Yes (virtual screening)	[72]
Pompe disease (OMIM# 232300)	GAA	1-(3,4-dimethoxybenzyl)-6-propyl-2-thioxo-2,3,5,6,7,8-hexahydropyrimido[4,5-d]pyrimidin-4(1H)-one (ML247 or NCGC00183885)		No	[79,80]
		N-acetylcysteine		Yes (co-crystallization)	[81,82]
		N-butyl-l-deoxynojirimycin (l-NBDNJ)		No	[83]
Krabbe disease (OMIM# 245200)	GALC	α-Lobeline		No	[91,92]
		3′,4′,7-trihydroxyisoflavone		No	[92]
Phenylketonuria (OMIM# 261600)	PAH	(6R)-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4)		Yes (co-crystallization)	[107,108]
Congenital erythropoietic porphyria (OMIM# 263700)	UORIIIS	Ciclopirox		Yes (virtual screening, NMR-based experiments)	[112]
Methylmalonic aciduria cblB type (OMIM# 251110)	ATR	N-(((4-chlorophenyl)carbamothioyl)amino)- 2-phenylacetamide		Yes (molecular docking)	[118,119]
Phosphomannomutase 2 deficiency (OMIM# 212065)	PMM2	1-(3-chlorophenyl)-3,3-bis(pyridin-2-yl)urea		No	[127]