Table 2.

Selected compounds as potential therapies for ADPKD in preclinical studies

Compounds	Classification	Key mechanism (target/pathway)	Animal models	Main effects	Ongoing clinical trials	References
Bosutinib (SKI-606)	Src kinase inhibitors	Src tyrosine kinase/EGFR	BPK mice, PCK rat, Pkd1+/− mice	Reduce renal cyst number and volume; decrease BUN	Yes	[32, 58]
Triptolide	Diterpenoids	PC2 (agonist)	Pkd1 cKO mice	Reduce renal cyst number and BUN	Yes	[61–63]
Statins	HMG-CoA reductase inhibitors	Farnesyl pyrophosphate	Han: SPRD rat	Reduce renal cystic index and BUN	Yes	[99–101]
Sorafinib, Plx5568	Raf inhibitors	B-Raf/MEK/ERK	Pkd2 cKO mice, Han:SPRD rat	Paradoxically increase liver cysts and augment renal and liver fibrosis	No	[14, 68]
R-roscovitine, S-CR8	Cyclin-dependent kinase inhibitors	Cyclin-dependent kinases	cpk mice, jck mice, Pkd1 cKO mice	Reduce renal and hepatic cystic indexes; decrease BUN	No	[26, 69]
TSA,VPA	HDAC inhibitors	Modify chromatin and gene expression (epigenetic control)	Pkd1 & Pkd2 cKO mice, pkd2 zebrafish morphants	Reduce renal cystic index and BUN	No	[71, 72]
Tetrazolo-CFTR(inh)-172,Ph-GlyH-101	CFTR inhibitors	CFTR chloride secretion	Pkd1 cKO mice	Decrease renal cyst number and BUN	No	[28]
Metformin	Biguanides	mTOR/CFTR (AMPK agonist)	Pkd1 cKO mice	Decrease renal cystic index	No	[79]
Genz-123346	Glucosylceramide inhibitors	Akt/mTOR	pcy mice, jck mice, Pkd1 cKO mice	Decrease renal cystic volume, fibrosis, and BUN	No	[31]
Pioglitazone, Rosiglitazone	Thiazolidinediones	PPAR-γ receptor/ CFTR	PCK rat, Han: SPRD rat	Decrease liver and renal cystic index	No	[68, 82]
Curcumin	Curcuminoids	mTOR, WNT, STAT3	Pkd1 cKO mice	Reduce renal cystic index and BUN	No	[24]
Ginkgolide B	Terpenoids	Unknown	Pkd1 cKO mice	Reduce renal cystic index but not hepatic cystic index	No	[88]
R-568	Calcimimetics	CaSR/intracellular Ca2+	Han: SPRD rat	Reduce renal cystic index, fibrosis and BUN	No	[90]
A-438079	P2X7 receptor antagonists	Purinergic pathway/ ERK	pkd2 zebrafish morphants	Reduce pronephric cyst formation	No	[94]
Pyrimethamine, S3I-201	Dihydrofolate reductase inhibitors	STAT3	Pkd1 cKO mice	Reduce renal cystic index and creatinine	No	[95]
Leflunomide	Pyrimidine synthesis inhibitors	STAT6	Bpk mice	Reduce renal cystic kidney and BUN	No	[97]

BUN, blood urea nitrogen; CaSR, Calcium-sensing receptor; CFTR, cystic fibrosis transmembrane conductance regulator; cKO, conditional knockout; HMG-CoA, 3-hydroxy-3-methylglutaryl–coenzyme A; PPAR-γ, Peroxisome proliferator-activated receptor γ; STAT, signal transducer and activator of transcription; TSA, Trichostatin A; VPA, Valproic acid.