 Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C28H31F3KN5O4S |
| Molecular Weight | 629.73535656929 |
| Exact Mass | 629.168 |
| Elemental Analysis | C, 53.40; H, 4.96; F, 9.05; K, 6.21; N, 11.12; O, 10.16; S, 5.09 |
| CAS # | 2204245-47-4 |
| Related CAS # | 2204245-48-5; 2204245-47-4 (potassium); |
| PubChem CID | 134687598 |
| Appearance | Typically exists as solid at room temperature |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 42 |
| Complexity | 1050 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | [K+].S(C1C=CC=CC=1)([N-]C(C1=CC=C(N2C=CC(=N2)OCCC2(C(F)(F)F)CC2)N=C1N1C[C@@H](C)CC1(C)C)=O)(=O)=O |
| InChi Key | BWMSVLSYIQHCQP-FYZYNONXSA-M |
| InChi Code | InChI=1S/C28H32F3N5O4S.K/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);/q;+1/p-1/t19-;/m0./s1 |
| Chemical Name | potassium;benzenesulfonyl-[6-[3-[2-[1-(trifluoromethyl)cyclopropyl]ethoxy]pyrazol-1-yl]-2-[(4S)-2,2,4-trimethylpyrrolidin-1-yl]pyridine-3-carbonyl]azanide |
| Synonyms | Bamocaftor potassium; VX-659 potassium; VX-659 potassium salt; Bamocaftor potassium [USAN]; 2204245-47-4; UNII-VY7D8MTV72; VY7D8MTV72; Bamocaftor potassium (USAN); |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | CFTR/cystic fibrosis transmembrane conductance regulator |
| ln Vitro | Bamocaftor is a CFTR corrector intended to repair the function of the F508del-CFTR protein [1]. |
| 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]. |
| References |
[1]. Emerging Cystic Fibrosis Transmembrane Conductance Regulator Modulators as New Drugs for Cystic Fibrosis: A Portrait of in Vitro Pharmacology and Clinical Translation. ACS Pharmacol Transl Sci. 2019 Oct 2;3(1):4-10. |
| Additional Infomation | Pharmacological correction of the defective ion channel with cystic fibrosis transmembrane conductance regulator (CFTR) has become an attractive approach to therapy directed at the root cause of the life-limiting disease cystic fibrosis (CF). CFTR defects range from absence, misfolding, and resulting degradation to functional defects of the CFTR protein. The discovery and development of the CFTR potentiator ivacaftor was a major break-through in CF therapy and has triggered an enormous incentive for seeking effective modulators such as lumacaftor, tezacaftor or elexacaftor for all patients with CF. A number of emerging CFTR modulators are currently in the development pipeline, and rescue levels of CFTR protein approach a cure for cystic fibrosis. In this review, we identify and characterize all preclinical and clinical emerging CFTR modulators and discuss the in vitro pharmacology, looking at CFTR protein expression and chloride transport and the translation to the clinic. The new emerging CFTR modulators could offer new therapeutic solutions for CF patients.[1] |
Solubility Data
| Solubility (In Vitro) | Typically soluble in DMSO (e.g. 10 mM) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5880 mL | 7.9398 mL | 15.8796 mL | |
| 5 mM | 0.3176 mL | 1.5880 mL | 3.1759 mL | |
| 10 mM | 0.1588 mL | 0.7940 mL | 1.5880 mL |