(R)-Elexacaftor is an enantiomer of Elexacaftor (HY-111772). (R)-Elexacaftor is the Compound 37 from patent WO2018107100A1. (R)-Elexacaftor is a modulator of cystic fibrosis transmembrane conductance regulator (CFTR), the EC50 for CFTR dF508 is 0.29 uM[1].
CFTR corrector 1 (compound 1) is a modulator of cystic fibrosis transmembrane conductance regulator (CFTR). CFTR corrector 1 (compound 1) facilitates the processing and trafficking of CFTR to increase the amount of CFTR at the cell surface[1].
Astressin 2B is a potent and selective corticotropin-releasing factor receptor 2 (CRF2) antagonist, with the IC50 values of 1.3 nM and > 500 nM for CRF2 and CRF1, respectively. Astressin 2B antagonizes CRF2-mediated inhibition of gastric emptying[1][2][3].
CRF1 receptor antagonist-1 (Compound 2) is a CRF1 receptor antagonist. CRF1 receptor antagonist-1 can be used for research of congenital adrenal hyperplasia (CAH)[1].
SRI-37240 is a potent premature termination codons (PTCs) inhibitor. SRI-37240 suppresses CFTR nonsense mutations. SRI-37240 alters cellular translation termination at PTCs in HEK293T cells. SRI-37240 can also restore CFTR function in primary bronchial epithelial cells when combination with G418[1].
GLPG1837 is a potent and reversible CFTR potentiator, with EC50s of 3 nM and 339 nM for F508del and G551D CFTR, respectively.
VX-661 is a second F508del CFTR corrector and help CFTR protein reach the cell surface.
KM11060 is a novel corrector of the F508del-CFTR trafficking defect.Target: CFTRin vitro: Small-molecule correctors such as KM11060 may serve as useful pharmacological tools in studies of the F508del-CFTR processing defect and in the development of cystic fibrosis therapeutics. KM11060 rescues F508del-CFTR trafficking in cultured cells and native epithelial tissues. KM11060 partially corrects F508del-CFTR processing and increases surface expression to 75% of that observed in cells incubated at low temperature. Up to 50% of the F508del-CFTR in cells treated with KM11060 was complex-glycosylated, indicating passage through the Golgi. KM11060 as a promising compound for further development of CF therapeutics. [1]in vivo: In LPS-induced acute lung inflammation, blockade of PSGL-1 (P-selectin glycoprotein ligand-1) or P-selectin, antagonism of PAF by WEB2086, or correction of mutated CFTR trafficking by KM11060 could significantly increase plasma lipoxin A4 levels in F508del relevant to wildtype mice. [2]
GLPG2451 is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator, which effectively potentiates low temperature rescued F508del CFTR with an EC50 of 11.1 nM[1].
PG01 is a potent CFTR Cl- channel potentiator. PG01 can correct gating defects of CFTR mutants, is effective on b>E193K, G970R and G551D (CFTR mutants) with Kd values of 0.22 μM, 0.45 μM and 1.94 μM, respectively. PG01 is also effective on ΔF508 (Ka of 0.3 μM). PG01 increases ΔF508-CFTR Cl- current after adding Forskolin[1][2].
SRI-41315 is a small molecule that induces translational readthrough of CFTR nonsense mutations by eRF1 depletion, restores CFTR expression and function, suppresses CFTR nonsense mutations.SRI-41315 induces translational readthrough by depleting eRF1 protein level and prolonging the translational pause that occurs at premature termination codons (PTCs).SRI-41315 reduced eRF1 levels in a manner dependent upon a ubiquitin-mediated proteasome degradation pathway.SRI-41315 in combination with G418 restores CFTR function in primary bronchial epithelial cells derived from a CF patient with CFTR nonsense alleles.
GlyH-101 is a cell-permeable glycinyl hydrazone compound that blocks CFTR with Ki of 1.4 uM.IC50 value: 1.4 uM (Ki, at +60 mV) [1]Target: CFTRin vitro: GlyH-101 reversibly inhibited CFTR Cl- conductance in <1 min. Whole-cell current measurements revealed voltage-dependent CFTR block by GlyH-101 with strong inward rectification, producing an increase in apparent inhibitory constant Ki from 1.4 microM at +60 mV to 5.6 microM at -60 mV. GlyH-101 inhibitory potency was independent of pH from 6.5-8.0, where it exists predominantly as a monovalent anion with solubility approximately 1 mM in water[1]. In HeLa cells, these events were associated with a decrease in the rate of oxygen consumption, with GlyH-101 demonstrating a higher potency than CFTR(inh)-172. The impact of CFTR inhibitors on inflammatory parameters was also tested in HeLa cells. CFTR(inh)-172, but not GlyH-101, induced nuclear translocation of nuclear factor-kappaB (NF-kappaB) [2]. GlyH-101 is a glycine hydrazide that has recently been shown to block CFTR channels but its effects on cardiomyocytes are unknown. Here the action of GlyH-101 on cardiac I(Cl.PKA) and on other ion currents has been established. Whole-cell patch-clamp recordings were made from rabbit isolated ventricular myocytes. GlyH-101 blocked I(Cl.PKA) in a concentration- and voltage-dependent fashion (IC(50) at +100 mV=0.3 ± 1.5 μM and at -100 mV=5.1 ± 1.3 μM) [3].in vivo: Topical GlyH-101 (10 microM) in mice rapidly and reversibly inhibited forskolin-induced hyperpolarization in nasal potential differences. In a closed-loop model of cholera, intraluminal GlyH-101 (2.5 microg) reduced by approximately 80% cholera toxin-induced intestinal fluid secretion [1].
Ivacaftor is a potent and orally bioavailable CFTR potentiator, targeting G551D-CFTR and F508del-CFTR with EC50s of 100 nM and 25 nM, respectively.
CFTR corrector 4 (Compound 13), an active (R,R)-form enantiomer, is a highly potent and orally active cystic fibrosis transmembrane conductance regulator (CFTR) corrector. CFTR corrector 4 can increase CFTR levels at the cell surface and have the potential for treatment of cystic fibrosis[1].
CFTR corrector 8 is a potent CFTR modulator. CFTR can be used in the research of cystic fibrosis[1].
BPO-27 racemate is a potent CFTR inhibitor with an IC50 of 8 nM.
GLPG-3221 is a potent, orally active corrector of CFTR (cystic fibrosis transmembrane conductance regulator), with an EC50 of 105 nM. GLPG-3221 can be uesd for the treatment of cystic fibrosis[1].
Olacaftor (VX-440, VX440) is a next-generation CFTR corrector, shows the potential to enhance the amount of CFTR protein at the cell’s surface and for treatment of cystic fibrosis. Fibrosis Phase 2 Clinical
Vanzacaftor is a modulator of cystic fibrosis transmembrane conductance regulator (CFTR) for treating cystic fibrosis.
Bamocaftor (VX-659) is a cystic fibrosis transmembrane conductance regulator (CFTR) corrector designed to restore F508del-CFTR protein function. Bamocaftor can be used combine with Tezacaftor and Ivacaftor in cystic fibrosis research[1].
Galicaftor (ABBV-2222; GLPG-2222) is a potent and orally active cystic fibrosis transmembrane conductance regulator (CFTR) corrector. Galicaftor can be used for cystic fibrosis research[1].
Chromanol 293B is a selective blocker of the slow delayed rectifier K+ current (IKs) with IC50 of 1-10 μM and a weak inhibitor of KATP channel. Chromanol 293B also blocks the CFTR chloride current with an IC50 of 19 μM[1].
PPQ-102 is a potent CFTR inhibitor which can completely inhibited CFTR chloride current with IC50 of ~90 nM. IC50 value: 90 nM [1]Target: CFTRin vitro: The most potent compound, 7,9-dimethyl-11-phenyl-6-(5-methylfuran-2-yl)-5,6-dihydro-pyrimido[4',5'-3,4]pyrrolo[1,2-a]quinoxaline-8,10-(7H,9H)-dione, PPQ-102, completely inhibited CFTR chloride current with IC(50) approximately 90 nM. The PPQs, unlike prior CFTR inhibitors, are uncharged at physiological pH, and therefore not subject to membrane potential-dependent cellular partitioning or block efficiency. Patch-clamp analysis confirmed voltage-independent CFTR inhibition by PPQ-102 and showed stabilization of the channel closed state [1]. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of (36)Cl(-) influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102 [2]. Airway epithelial NCI-H292 cells and primary cultures of noncystic fibrosis human airway epithelial cells were treated with cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors (CFTR-inh(172) or PPQ-102) or transfected with a CFTR small interfering (si)RNA with or without a selective epidermal growth factor receptor tyrosine kinase inhibitor [3].in vivo: PPQ-102 prevented cyst expansion and reduced the size of preformed cysts in a neonatal kidney organ culture model of polycystic kidney disease. PPQ-102 is the most potent CFTR inhibitor identified to date [1].
CFTR(inh)-172 is a potent and selective blocker of the CFTR chloride channel; reversibly inhibited CFTR short-circuit current in less than 2 minutes with a Ki of 300 nM.