Version May 2024
| CFTR modulator class | Drug names | Mechanism of action | Class(es) of CFTR mutation targeted* | CFTR mutations in this class (selected examples) |
| Potentiators |
| Help open the CFTR channel and increase the flux of chloride and bicarbonate across the apical cell surface. Potentiators target gating, conduction, and insufficient protein mutations. | Gating mutations (class III) – CFTR protein is created and moves to the cell surface but forms a channel that does not open properly. | Some missense and small deletion mutations such as G551D, S549N, and F508del (which also has defective protein processing and stability). |
| Conduction mutations (class IV) – CFTR protein is created and moves to the cell surface but with a malformed channel that limits the rate of chloride and bicarbonate movement. | Some missense mutations such as R117H, D1152H, and R347PE. | |||
| Insufficient protein mutations (class V) – CFTR protein is created that has normal processing, channel, and gating properties, but the amount of protein present at the cell surface is deficient. This can be caused by too little CFTR protein being produced or an increased rate of channel deactivation or removal from the cell surface. | Some missense and noncanonical splicing mutations such as 3849+10kbC→T, 2789+5G→A, 3272-26A→G, and F508del (which also has defective protein processing and gating). | |||
| Correctors |
| Help normalize the folding of defective CFTR protein and its movement to the cell surface. | Processing mutations (class II) – CFTR protein is created but misfolds, preventing it from reaching the apical cell surface. | Some missense and small deletion mutations such as F508del, N1303K, and I507del. |
| Amplifiers | No approved amplifiers | Increase expression of the abnormal CFTR mRNA and production of CFTR protein. | Processing, gating, conduction, or insufficient protein mutations (class II-V) – A channel is created that retains at least some functional CFTR channel activity either at baseline or following exposure to other classes of CFTR modulators. | Any of the above mutations. |
| Stabilizers | No approved stabilizers | Limit removal and degradation of CFTR protein from the cell surface. | ||
| Other terms used to classify CFTR mutations | Definition | CFTR mutations in this category (selected examples) | ||
| Residual function mutations | Mutations that retain some CFTR function and are often associated with a milder CFTR phenotype. These mutations usually respond to potentiators (eg, elexacaftor, ivacaftor). | R117H, 3849+10kbC→T, 2789+5G→A, D1152H, 3272-26A→G, L206W, A455E. | ||
| Minimal function mutations | Mutations that have negligible function at baseline and do not respond to approved CFTR modulators. | Nonsense mutations, canonical splicing mutations, major duplications or deletions, and some missense mutations. | ||
CFTR: cystic fibrosis transmembrane conductance regulator; mRNA: messenger ribonucleic acid.
* CFTR mutations can be categorized by the type of defects they cause in CFTR biosynthesis, intracellular processing, channel activity, and/or protein stability. This classification scheme is an oversimplification because some variants lead to more than 1 class of CFTR dysfunction.
¶ Elexacaftor appears to function as both a corrector (which works synergistically with tezacaftor) and as a potentiator (which works synergistically with ivacaftor)[2].آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
