Second-Generation Pharmacological Chaperones: Beyond Inhibitors
Abstract
:1. Introduction
2. Second-Generation Pharmacological Chaperones against LSDs
2.1. Gaucher Disease
2.2. Fabry Disease
2.3. Pompe Disease
2.4. Krabbe Disease
3. Non-Inhibitory Pharmacological Chaperones for Miscellaneous Conformational Diseases
3.1. Phenylketonuria
3.2. Congenital Erythropoietic Porphyria
3.3. Methylmalonic Aciduria (MMA) Cdlb Type
3.4. Phosphomannomutase 2 Deficiency
4. Conclusions
Funding
Conflicts of Interest
References
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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] |
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Tran, M.L.; Génisson, Y.; Ballereau, S.; Dehoux, C. Second-Generation Pharmacological Chaperones: Beyond Inhibitors. Molecules 2020, 25, 3145. https://doi.org/10.3390/molecules25143145
Tran ML, Génisson Y, Ballereau S, Dehoux C. Second-Generation Pharmacological Chaperones: Beyond Inhibitors. Molecules. 2020; 25(14):3145. https://doi.org/10.3390/molecules25143145
Chicago/Turabian StyleTran, My Lan, Yves Génisson, Stéphanie Ballereau, and Cécile Dehoux. 2020. "Second-Generation Pharmacological Chaperones: Beyond Inhibitors" Molecules 25, no. 14: 3145. https://doi.org/10.3390/molecules25143145