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Identification of drug repurposing candidates for the treatment of polycystic kidney disease - Salicylic acid

ABSTRACT: Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease with limited treatment options. Drug repurposing offers a promising strategy to find effective treatments. We identified birinapant, bardoxolone methyl and salicylic acid as repurposing candidates for ADPKD and applied thermal proteome profiling to identify disease-relevant targets. Our results uncovered shared effects between the three drugs, including a thermal shift in ADP/ATP translocases (SLC25A4/5/6) caused by reduced ATP production. As expected, salicylic acid displayed a polypharmacological profile but also engaged enzymes along the N-linked glycosylation pathway and inhibited PTK2, an activator of the proliferative PI3K/Akt/mTOR pathway. Orthogonal assays and computational modelling confirmed these findings and located the binding site (499-504) of salicylic acid within PTK2’s ATP-binding pocket. Engagement of several targets was achieved at clinically relevant concentrations. We have identified novel targets of three repurposing candidates that contribute to the cyst growth reducing effects in preclinical ADPKD models and identify salicylic acid, the metabolite of aspirin, as the repurposing candidate with the most promising mechanisms of action.This dataset contains files from thermal proteome profiling after salicylic acid exposure.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Kidney

SUBMITTER: Alina Meyer

LAB HEAD: Per Artursson

PROVIDER: PXD063666 | Pride | 2026-05-18

REPOSITORIES: Pride

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			Action	DRS
	20231011_05_AM_TPP_S1_F6_01.raw	Raw
	20231011_07_AM_TPP_S1_F1_01.raw	Raw
	20231011_09_AM_TPP_S1_F2_01.raw	Raw
	20231011_101_AM_TPP_S4_F10_01.raw	Raw
	20231011_103_AM_TPP_S4_F11_01.raw	Raw

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Identification of drug repurposing candidates for the treatment of polycystic kidney disease - Bardoxolone methyl

Project description:Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease with limited treatment options. Drug repurposing offers a promising strategy to find effective treatments. We identified birinapant, bardoxolone methyl and salicylic acid as repurposing candidates for ADPKD and applied thermal proteome profiling to identify disease-relevant targets. Our results uncovered shared effects between the three drugs, including a thermal shift in ADP/ATP translocases (SLC25A4/5/6) caused by reduced ATP production. As expected, salicylic acid displayed a polypharmacological profile but also engaged enzymes along the N-linked glycosylation pathway and inhibited PTK2, an activator of the proliferative PI3K/Akt/mTOR pathway. Orthogonal assays and computational modelling confirmed these findings and located the binding site (499-504) of salicylic acid within PTK2’s ATP-binding pocket. Engagement of several targets was achieved at clinically relevant concentrations. We have identified novel targets of three repurposing candidates that contribute to the cyst growth reducing effects in preclinical ADPKD models and identify salicylic acid, the metabolite of aspirin, as the repurposing candidate with the most promising mechanisms of action. This dataset contains files from thermal proteome profiling after bardoxolone methyl exposure.

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Identification of drug repurposing candidates for the treatment of polycystic kidney disease - RPTEC/TERT1 proteome

Project description:Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease with limited treatment options. Drug repurposing offers a promising strategy to find effective treatments. We identified birinapant, bardoxolone methyl and salicylic acid as repurposing candidates for ADPKD and applied thermal proteome profiling to identify disease-relevant targets. Our results uncovered shared effects between the three drugs, including a thermal shift in ADP/ATP translocases (SLC25A4/5/6) caused by reduced ATP production. As expected, salicylic acid displayed a polypharmacological profile but also engaged enzymes along the N-linked glycosylation pathway and inhibited PTK2, an activator of the proliferative PI3K/Akt/mTOR pathway. Orthogonal assays and computational modelling confirmed these findings and located the binding site (499-504) of salicylic acid within PTK2’s ATP-binding pocket. Engagement of several targets was achieved at clinically relevant concentrations.We have identified novel targets of three repurposing candidates that contribute to the cyst growth reducing effects in preclinical ADPKD models and identify salicylic acid, the metabolite of aspirin, as the repurposing candidate with the most promising mechanisms of action.This dataset contains files from the global protein analysis of RPTEC/TERT1 cells cultured on TC-inserts under physiological (10%; PO) and atmospheric (21%; AO) oxygen tension.

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