Table 2.

Ongoing development of ENaC therapeutics

Drug	Type	Mechanism	Current Stage of Development
NVP-QBE 170 (Novartis)	Small molecule	Direct inhibition	Preclinical Models [66]
AZD 5634 (AstraZeneca)	Small molecule	Direct inhibition	Phase I Clinical Trial clinicaltrials.gov: NCT02950805
VX-371 (formerly P-1037, collaboration between Vertex and Parion)	Small molecule	Direct inhibition	Phase II Clinical Trial (combination VX-371 and Orkambi in F508del homozygotes); clinicaltrials.gov: NCT02709109
QBW276 (Novartis)	Small molecule	Direct inhibition	Phase II Clinical Trials; clinicaltrials.gov: NCT02566044
BI 443651 (Boehringer INgelheim)	Small molecule	Direct inhibition	Phase I Clinical Trial; clinicaltrials.gov: NCT02566044
QUB-TL1	Small molecule	Channel-Activating Protease inhibitor	Preclinical Models [74]
MK 104 (Mucokinetica)	Small molecule	Channel-Activating Protease inhibitor	Preclinical Models { Hall, abstract in J Cyst Fibros 2016, 15:S4-S5; R Hall, abstract in Pediatr Pulmonol 2017, 52:S239-S240}
ARO-ENaC	Molecular inhibition	Small interfering RNA	Preclinical Models {EW Bush abstract in Am J Respir Crit Care Med 2018, 197:A3867}
siRNA	Molecular inhibition	Small interfering RNA	Preclinical Models [55]
ENaC Inhibitory ASO (Ionis)	Molecular inhibition	Antisense oligonucleotide	Preclinical Models [81]
SPX-101 (Spyryx)	Peptide analogue	Indirect inhibition as a SPLUNC-1 analogue, which promotes ENaC channel internalization	Phase II Clinical Trial [53][72]; clinicaltrials.gov: NCT03229252