f508del-cftr

Lumacaftor (VRT 826809) is a CFTR modulator that corrects the folding and trafficking of CFTR protein. It enhances F508del-CFTR protein maturation in FRT cells (EC50: 100 nM).

Bamocaftor is a CFTR channel (DeltaF508-CFTR mutation) corrector for CF transmembrane conductance regulators designed to restore F508del-CFTR protein function. Combined use of tezacaftor and VX-561 for the treatment of cystic fibrosis patients with F508del MF.

VRT-532 (CFpot-532) is an effective modulator of CFTR and is commonly used in studies of cystic fibrosis (CF) caused by CFTR defects. Modification of CFTR by this small molecule modulator can increase arylsulfatase B (ARSB), which is necessary to reduce the accumulation of sulphate glycosaminosaccharide (gag), thus reducing the accumulation of 4-chondroitin sulfate in cystic fibrosis.

Ivacaftor (VX-770) (VX-770) is a potentiator of CFTR targeting G551D-CFTR (EC50: 100 nM) and F508del-CFTR (EC50: 25 nM) in Fisher rat thyroid cells, respectively.

CFTR corrector 2 (FDL169) is a novel and potent CFTR (Cystic fibrosis transmembrane conductance regulator) corrector for treating cystic fibrosis (CF) patients who carry the F508del mutation.

PG01 is a potent CFTR Cl-channel potentiator, effective against ΔF508 (Ka 0.3 μM), and also against E193K, G970R and G551D (CFTR mutants), with Kd values of 0.22 μM, 0.45 μM and 1.94 μM, respectively.PG01 increases ΔF508-CFTR Cl- currents upon addition of forskolin. F508-CFTR Cl-current upon addition of Forskolin, correcting the gating defect of CFTR mutants.

GLPG1837 (ABBV-974) is an effective CFTR potentiator, with EC50s of 3 nM and 339 nM for F508del and G551D CFTR, respectively.

CFTR Corrector 15 (Compound 4172) serves as a corrector for cystic fibrosis transmembrane conductance regulator (CFTR). When used in combination with VX-809, it addresses the folding defects of F508del-CFTR. CFTR Corrector 15 is also applicable in the research of cystic fibrosis.

ARN23765 is an F508del-CFTR corrector with an EC50 of 38 pM in human bronchial epithelial cells. It enhances the maturation and function of F508del-CFTR at the cell membrane, influencing ion transport and secretion, thereby addressing the pathological mechanisms of cystic fibrosis (CF).

(Rac)-Tezacaftor ((Rac)-VX-661) is a racemic mixture of the F508del CFTR corrector, Tezacaftor, used in cystic fibrosis research [1].

RNF5 agonist 1 (analog-1), a structural analog of the RNF5 inhibitor inh-02, is a potent RNF5 agonist. In CFBE41o- cells expressing F508del-CFTR, RNF5 agonist 1 enhances the ubiquitination of ATG4B.

Icenticaftor (QBW251) is an orally active potentiator of the CFTR channel.

RNF5 inhibitor inh-02, a potent E3 ubiquitin ligase RNF5/RMA1 inhibitor, demonstrates significant efficacy in rescuing F508del-CFTR with an EC50 of 2.2 uM in bronchial epithelial cells homozygous for the F508del mutation. This compound is valuable for cystic fibrosis research[1].

GLPG2451 is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator that effectively enhances the function of low-temperature-rescued F508del CFTR with an EC50 of 11.1 nM.

KM11060 is a novel corrector of the F508del-CFTR trafficking defect, Correcting F508del-CFTR trafficking, increasing the amount of functional CFTR at the plasma membrane.

PGD97 is a selective cyclic peptide inhibitor targeting the CAL CFTR interaction, with its desulfurization-cyclized form exhibiting a KD value of 6 nM for the CAL PDZ domain. It shows a selectivity of at least 130-fold over the NHERF1 2 PDZ domains. PGD97 stabilizes F508del-CFTR on the cell membrane, enhancing CFTR function necessary for normal pulmonary fluid balance. This compound is applicable in cystic fibrosis research.

C4 Ceramide is a bioactive sphingolipid and cell-permeable analog of naturally occurring ceramides. [1] [2] [3] It inhibits IL-4 production by 16% in EL4 T cells stimulated with phorbol 12-myristate 13-acetate when used at a concentration of 10 μM. [1] C4 Ceramide is cytotoxic to SK-BR-3 and MCF-7/Adr breast cancer cells (IC50s = 15.9 and 19.9 μM, respectively). [2] C4 Ceramide also increases maturation and stability of cystic fibrosis transmembrane conductance regulator (CFTR) proteins bearing the F508 deletion (F508del) mutation, enhances cAMP-activated chloride secretion, and suppresses secretion of IL-8 in primary epithelial cells isolated from patients with cystic fibrosis.[3]