Small-molecule inhibitor of intestinal anion exchanger SLC26A3 for treatment of hyperoxaluria and nephrolithiasis

Çil, Onur; Chu, Tifany; Haggie, Peter M.

doi:10.1172/jci.insight.153359

Cited by 14 publications

(9 citation statements)

References 48 publications

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“…Over the past decade, researchers have suggested that SLC26A3 may serve as a therapeutic target to treat hyperoxaluria and prevent CaOx urolithiasis. CIL et al (2022) demonstrated that DRAinh-A270 selectively inhibits SLC26A3-mediated chloride/bicarbonate exchange. Notably, the same study reported that the reduced function of SLC26A3 mutants, which may decrease male fertility, may be caused by a weakened interaction between the specific structural domain STAS and the cystic fibrosis transmembrane conductance-regulated channel, thereby affecting chloride transport.…”

Section: Slc26 Proteins In the Kidneymentioning

confidence: 97%

SLC26 family: a new insight for kidney stone disease

Huang

Liu

et al. 2023

Front. Physiol.

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The solute-linked carrier 26 (SLC26) protein family is comprised of multifunctional transporters of substrates that include oxalate, sulphate, and chloride. Disorders of oxalate homeostasis cause hyperoxalemia and hyperoxaluria, leading to urinary calcium oxalate precipitation and urolithogenesis. SLC26 proteins are aberrantly expressed during kidney stone formation, and consequently may present therapeutic targets. SLC26 protein inhibitors are in preclinical development. In this review, we integrate the findings of recent reports with clinical data to highlight the role of SLC26 proteins in oxalate metabolism during urolithogenesis, and discuss limitations of current studies and potential directions for future research.

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Section: Slc26 Proteins In the Kidneymentioning

confidence: 97%

SLC26 family: a new insight for kidney stone disease

Huang

Liu

et al. 2023

Front. Physiol.

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“…Ions, amino acids and their transporters and channels, calcium-sensitive receptor signaling pathways, and the metabolic pathways of vitamin D, oxalic acid, cysteine, purine and uric acid are considered to play key roles in the etiology of kidney stones ( 42 ). CaOx stones formed due to hyperoxaluria account for approximately two-thirds of all kidney stones ( 43 ). In HK-2 cells, oxalate activates ERS/ROS via NF-κB-dependent pathways, causing autophagy, apoptosis and mitochondrial damage ( 44 ).…”

Section: The Various Forms Of Cell Death and Urolithiasismentioning

confidence: 99%

Cell death‑related molecules and targets in the progression of urolithiasis (Review)

Wu,

Xue,

et al. 2024

Int J Mol Med

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Urolithiasis is a high-incidence disease caused by calcium oxalate (mainly), uric acid, calcium phosphate, struvite, apatite, cystine and other stones. The development of kidney stones is closely related to renal tubule cell damage and crystal adhesion and aggregation. Cell death, comprising the core steps of cell damage, can be classified into various types (i.e., apoptosis, ferroptosis, necroptosis and pyroptosis). Different crystal types, concentrations, morphologies and sizes cause tubular cell damage via the regulation of different forms of cell death. Oxidative stress caused by high oxalate or crystal concentrations is considered to be a precursor to a variety of types of cell death. In addition, complex crosstalk exists among numerous signaling pathways and their key molecules in various types of cell death. Urolithiasis is considered a metabolic disorder, and tricarboxylic acid cycle-related molecules, such as citrate and succinate, are closely related to cell death and the inhibition of stone development. However, a literature review of the associations between kidney stone development, metabolism and various types of cell death is currently lacking, at least to the best of our knowledge. Thus, the present review summarizes the major advances in the understanding of regulated cell death and urolithiasis progression.

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“…4,5 To prevent stone recurrence, lifestyle changes and preventive medical treatment are used. 6 Hyperoxaluria is a major risk factor for calcium oxalate stones, 7 the most common type constituting 2/3 of all kidney stones. 8 Currently, medical treatment options for kidney stones are limited and there are no approved treatments for hyperoxaluria.…”

Section: Introductionmentioning

confidence: 99%