Table 1. Mechanism of action and targets of emerging cystic fibrosis transmembrane conductance regulator (CFTR) modulators

Mutation class	Nature of defect	Example mutations	Pancreatic function^#	Modulator strategy	Agents in development
I	Biosynthesis	G542X	Insufficient	Suppressor Suppressor and potentiator^¶	Ataluren
II	Trafficking	F508del	Insufficient	Corrector Corrector plus potentiator	VX-809 plus ivacaftor⁺ VX-661 plus ivacaftor⁺
III	Channel gating	G551D	Insufficient	Potentiator	Ivacaftor (FDA approved, G551D) Other gating mutations?^¶
IV	Channel conductance	R117H	Sufficient	Potentiator?^¶	No clinical data available
V	Low transcript levels	3849+10kb C->T	Sufficient	Potentiator?^¶	No clinical data available

FDA: US Food and Drug Administration. ^#: when in trans with a non-functional CFTR mutation; ^¶: theoretical approach based on nature of defect and known drug mechanism; ⁺: currently in phase II trials. Reproduced from [15] with permission from the publisher.