Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386567609> ?p ?o ?g. }
- W4386567609 endingPage "115445" @default.
- W4386567609 startingPage "115445" @default.
- W4386567609 abstract "Variants in SLC26A4 (pendrin) are the most common reasons for genetic hearing loss and vestibular dysfunction in East Asians. In patients with Pendred syndrome and DFNB4 (autosomal recessive type of genetic hearing loss 4), caused by variants in SLC26A4, the hearing function is residual at birth and deteriorates over several years, with no curative treatment for these disorders. In the present study, we revealed that a novel small molecule restores the expression and function of mutant pendrin. High-throughput screening of 54,000 small molecules was performed. We observed that pendrin corrector (PC2-1) increased the surface expression and anion exchange activity of p.H723R pendrin (H723R-PDS), the most prevalent genetic variant that causes Pendred syndrome and DFNB4. Furthermore, in endogenous H723R-PDS-expressing human nasal epithelial cells, PC2-1 significantly increased the surface expression of pendrin. PC2-1 exhibited high membrane permeability in vitro and high micromolar concentrations in the cochlear perilymph in vivo. In addition, neither inhibition of Kv11.1 activity in the human ether-a-go-go-related gene assay nor cell toxicity in the cell proliferation assay was observed at a high PC2-1 concentration (30 μM). These preclinical data support the hypothesis of the druggability of mutant pendrin using the novel corrector molecule PC2-1. In conclusion, PC2-1 may be a new therapeutic molecule for ameliorating hearing loss and treating vestibular disorders in patients with Pendred syndrome or DFNB4." @default.
- W4386567609 created "2023-09-10" @default.
- W4386567609 creator A5002761429 @default.
- W4386567609 creator A5007871609 @default.
- W4386567609 creator A5011007448 @default.
- W4386567609 creator A5011363633 @default.
- W4386567609 creator A5016925161 @default.
- W4386567609 creator A5021284354 @default.
- W4386567609 creator A5034176785 @default.
- W4386567609 creator A5034732409 @default.
- W4386567609 creator A5034765579 @default.
- W4386567609 creator A5057025466 @default.
- W4386567609 creator A5070506137 @default.
- W4386567609 creator A5087966363 @default.
- W4386567609 date "2023-11-01" @default.
- W4386567609 modified "2023-10-18" @default.
- W4386567609 title "Novel small molecule-mediated restoration of the surface expression and anion exchange activity of mutated pendrin causing Pendred syndrome and DFNB4" @default.
- W4386567609 cites W1480384350 @default.
- W4386567609 cites W1562080471 @default.
- W4386567609 cites W1983746433 @default.
- W4386567609 cites W1988786406 @default.
- W4386567609 cites W2023471002 @default.
- W4386567609 cites W2028808636 @default.
- W4386567609 cites W2037454945 @default.
- W4386567609 cites W2040820498 @default.
- W4386567609 cites W2041838113 @default.
- W4386567609 cites W2045791307 @default.
- W4386567609 cites W2053606850 @default.
- W4386567609 cites W2071407356 @default.
- W4386567609 cites W2082372749 @default.
- W4386567609 cites W2082819975 @default.
- W4386567609 cites W2092890929 @default.
- W4386567609 cites W2095103362 @default.
- W4386567609 cites W2097880791 @default.
- W4386567609 cites W2105041673 @default.
- W4386567609 cites W2114254209 @default.
- W4386567609 cites W2116305393 @default.
- W4386567609 cites W2132267388 @default.
- W4386567609 cites W2132771736 @default.
- W4386567609 cites W2138261854 @default.
- W4386567609 cites W2148872965 @default.
- W4386567609 cites W2153767327 @default.
- W4386567609 cites W2158410921 @default.
- W4386567609 cites W2185791982 @default.
- W4386567609 cites W2191630905 @default.
- W4386567609 cites W2275041866 @default.
- W4386567609 cites W2344575936 @default.
- W4386567609 cites W2553015816 @default.
- W4386567609 cites W2566427422 @default.
- W4386567609 cites W2897626245 @default.
- W4386567609 cites W2919471085 @default.
- W4386567609 cites W2943585513 @default.
- W4386567609 cites W2965854178 @default.
- W4386567609 cites W2969524048 @default.
- W4386567609 cites W3049341660 @default.
- W4386567609 cites W3081843885 @default.
- W4386567609 cites W3140132982 @default.
- W4386567609 cites W3153906204 @default.
- W4386567609 cites W3192082558 @default.
- W4386567609 cites W3204787239 @default.
- W4386567609 cites W4210996550 @default.
- W4386567609 cites W4211056322 @default.
- W4386567609 cites W4299805930 @default.
- W4386567609 cites W4323531644 @default.
- W4386567609 doi "https://doi.org/10.1016/j.biopha.2023.115445" @default.
- W4386567609 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37690388" @default.
- W4386567609 hasPublicationYear "2023" @default.
- W4386567609 type Work @default.
- W4386567609 citedByCount "0" @default.
- W4386567609 crossrefType "journal-article" @default.
- W4386567609 hasAuthorship W4386567609A5002761429 @default.
- W4386567609 hasAuthorship W4386567609A5007871609 @default.
- W4386567609 hasAuthorship W4386567609A5011007448 @default.
- W4386567609 hasAuthorship W4386567609A5011363633 @default.
- W4386567609 hasAuthorship W4386567609A5016925161 @default.
- W4386567609 hasAuthorship W4386567609A5021284354 @default.
- W4386567609 hasAuthorship W4386567609A5034176785 @default.
- W4386567609 hasAuthorship W4386567609A5034732409 @default.
- W4386567609 hasAuthorship W4386567609A5034765579 @default.
- W4386567609 hasAuthorship W4386567609A5057025466 @default.
- W4386567609 hasAuthorship W4386567609A5070506137 @default.
- W4386567609 hasAuthorship W4386567609A5087966363 @default.
- W4386567609 hasConcept C104317684 @default.
- W4386567609 hasConcept C105702510 @default.
- W4386567609 hasConcept C126322002 @default.
- W4386567609 hasConcept C134018914 @default.
- W4386567609 hasConcept C149011108 @default.
- W4386567609 hasConcept C169760540 @default.
- W4386567609 hasConcept C185592680 @default.
- W4386567609 hasConcept C190041318 @default.
- W4386567609 hasConcept C2777399954 @default.
- W4386567609 hasConcept C2778500370 @default.
- W4386567609 hasConcept C2779134260 @default.
- W4386567609 hasConcept C2780130748 @default.
- W4386567609 hasConcept C2780493683 @default.
- W4386567609 hasConcept C2780865074 @default.
- W4386567609 hasConcept C54355233 @default.
- W4386567609 hasConcept C548259974 @default.