| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
CFTR/cystic fibrosis transmembrane conductance regulator
CFTR (cystic fibrosis transmembrane conductance regulator), specifically the F508del mutant and other CFTR processing mutants. Bamocaftor is a CFTR corrector that binds to mutant CFTR protein and facilitates proper folding and trafficking to the cell surface, where it can function as a chloride channel. |
|---|---|
| ln Vitro |
Bamocaftor is a CFTR corrector intended to repair the function of the F508del-CFTR protein [1].
In vitro, Bamocaftor (VX-659) corrects the processing and trafficking defects of F508del-CFTR in cell-based assays. It increases the amount of mature CFTR protein at the cell surface and enhances CFTR-mediated chloride transport. When combined with tezacaftor and ivacaftor, VX-659 shows synergistic effects in restoring CFTR function in primary human bronchial epithelial cells from CF patients. |
| ln Vivo |
Presently, elexacaftor (VX-445) and bamocaftor (VX-659) are two new compounds being tested in phase 3 trials. Both drugs are next-generation CFTR correctors designed to restore F508del-CFTR protein function in patients with CF when administered with tezacaftor and ivacaftor. Furthermore, positive data has been reported in CF patients who are heterozygous for the F508del CFTR mutation or have one minimal function (MF) mutation (F508del-MF). In the F508del-MF group, treatment with either ivacaftor + tezacaftor + elexacaftor or bamocaftor resulted in mean absolute improvements in ppFEV1 of 13.8 and 13.3 percentage points, respectively (P < 0.001). In the F508del cohort, patients received standard ivacaftor–tezacaftor treatment. In this cohort the addition of elexacaftor and bamocaftor resulted in an 11.0-point and 9.7-point rise in the percentage of predicted FEV1 (P < 0.001), respectively[1].
In vivo, Bamocaftor is under clinical investigation for cystic fibrosis. Phase 2 clinical trials have demonstrated that VX-659 in combination with tezacaftor and ivacaftor improves lung function (ppFEV1) in CF patients with one F508del allele and one minimal function allele. The compound has shown promising efficacy in clinical development as part of a triple combination therapy regimen. |
| Enzyme Assay |
CFTR corrector activity is assessed using cell-based assays with F508del-CFTR expressing cells (e.g., CFBE41o- or primary human bronchial epithelial cells). Cells are treated with Bamocaftor for 24-48 hours, and CFTR maturation is assessed by Western blot for the mature (band C) form of CFTR. CFTR function is measured by Ussing chamber analysis of chloride transport or by high-throughput membrane potential assays.
|
| Cell Assay |
Primary human bronchial epithelial cells (HBE) from CF patients homozygous for F508del or with other CFTR mutations are cultured at air-liquid interface. Cells are treated with Bamocaftor alone or in combination with tezacaftor and ivacaftor for 24-48 hours. CFTR-mediated chloride transport is measured by Ussing chamber electrophysiology. CFTR protein maturation is assessed by Western blot, and cell surface CFTR is detected by cell surface biotinylation.
|
| Animal Protocol |
Clinical trials in CF patients have evaluated Bamocaftor in combination with tezacaftor and ivacaftor. Patients receive the triple combination orally for 4 weeks or longer. The primary efficacy endpoint is the absolute change in ppFEV1 (percent predicted forced expiratory volume in 1 second) from baseline. Secondary endpoints include sweat chloride concentration, CFQ-R respiratory domain scores, and safety assessments.
|
| ADME/Pharmacokinetics |
Bamocaftor is an orally bioavailable CFTR corrector. Pharmacokinetic studies in clinical trials show dose-proportional exposure. The compound is metabolized primarily by CYP3A4. It is typically dosed in combination with tezacaftor and ivacaftor. Specific PK parameters (half-life, Cmax, AUC) are available from clinical trial reports and regulatory submissions (Vertex Pharmaceuticals).
|
| Toxicity/Toxicokinetics |
The most common side effects included increased sputum production, worsening of lung infections, hemoptysis, and fever. Overall, dual or triple therapy was well tolerated in all tezacaftor trials. Based on these results, a global regulatory application was submitted in 2019 for the triple therapy of elexacaftor + tezacaftor + ivacaftor. This submission represents an important step toward providing treatment for the cystic fibrosis (CF) patient population for whom no approved drugs are currently available, and will also significantly enhance efficacy in patients homozygous for the F508del CFTR mutation.
In clinical trials, the VX-659/tezacaftor/ivacaftor triple combination has been generally well-tolerated. Common adverse events include headache, nasopharyngitis, and diarrhea. Elevations in liver transaminases have been observed, requiring monitoring. The safety profile is similar to other CFTR modulators. Serious adverse events are uncommon. Long-term safety data are being collected in ongoing studies. |
| References | |
| Additional Infomation |
Bamocaftor (VX-659) is being studied in the clinical trial NCT03224351 (a study evaluating the safety and efficacy of VX-659 in combination therapy in patients with cystic fibrosis).
Bamocaftor (VX-659) is a CFTR corrector developed by Vertex Pharmaceuticals for cystic fibrosis. It is part of a triple combination therapy with tezacaftor and ivacaftor. Clinical trials have shown efficacy in CF patients with one F508del allele and one minimal function allele. As of the current information, VX-659 has not received FDA approval; the approved triple combination is elexacaftor/tezacaftor/ivacaftor (Trikafta/Kaftrio). The compound is for research use only in the context of this database. |
| Molecular Formula |
C28H32F3N5O4S
|
|---|---|
| Molecular Weight |
591.6450
|
| Exact Mass |
591.212
|
| Elemental Analysis |
C, 56.84; H, 5.45; F, 9.63; N, 11.84; O, 10.82; S, 5.42
|
| CAS # |
2204245-48-5
|
| Related CAS # |
2204245-47-4 (potassium);2204245-48-5;
|
| PubChem CID |
134393443
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| Appearance |
White to off-white solid powder
|
| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.622
|
| LogP |
5.71
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
41
|
| Complexity |
1040
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@H]1CC(N(C1)C2=C(C=CC(=N2)N3C=CC(=N3)OCCC4(CC4)C(F)(F)F)C(=O)NS(=O)(=O)C5=CC=CC=C5)(C)C
|
| InChi Key |
IGEOJNMYRZUKIK-IBGZPJMESA-N
|
| InChi Code |
InChI=1S/C28H32F3N5O4S/c1-19-17-26(2,3)35(18-19)24-21(25(37)34-41(38,39)20-7-5-4-6-8-20)9-10-22(32-24)36-15-11-23(33-36)40-16-14-27(12-13-27)28(29,30)31/h4-11,15,19H,12-14,16-18H2,1-3H3,(H,34,37)/t19-/m0/s1
|
| Chemical Name |
N-(benzenesulfonyl)-6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carboxamide
|
| Synonyms |
Bamocaftor; VX-659; 2204245-48-5; Bamocaftor [USAN]; VX659; UNII-8C7XEW3K7S; 8C7XEW3K7S; Bamocaftor (USAN);
|
| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~169.02 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.23 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6902 mL | 8.4509 mL | 16.9019 mL | |
| 5 mM | 0.3380 mL | 1.6902 mL | 3.3804 mL | |
| 10 mM | 0.1690 mL | 0.8451 mL | 1.6902 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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