| Identification | Back Directory | [Name]
2,2-bis(4-fluorophenyl)-2-phenyl-acetamide | [CAS]
289656-45-7 | [Synonyms]
ICA 17043
Senicapoc
ICA-17043;ICA 17043;ICA17043
2,2-bis(4-fluorophenyl)-2-phenyl-acetamide
4-Fluoro-A-(4-Fluorophenyl)-A-Phenyl-BenzeneacetaMide
Benzeneacetamide, 4-fluoro-α-(4-fluorophenyl)-α-phenyl-
Benzeneacetamide, 4-fluoro-a-(4-fluorophenyl)-a-phenyl-
4-Fluoro-alpha-(4-fluorophenyl)-alpha-phenylbenzeneacetamide | [Molecular Formula]
C20H15F2NO | [MDL Number]
MFCD09027349 | [MOL File]
289656-45-7.mol | [Molecular Weight]
323.34 |
| Chemical Properties | Back Directory | [Melting point ]
180-181 °C(Solv: hexane (110-54-3); dichloromethane (75-09-2)) | [Boiling point ]
460.7±45.0 °C(Predicted) | [density ]
1.250±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Store in freezer, under -20°C | [solubility ]
DMSO : 50 mg/mL (154.64 mM; Need ultrasonic) | [form ]
Powder | [pka]
15.41±0.50(Predicted) | [color ]
White to yellow | [InChI]
InChI=1S/C20H15F2NO/c21-17-10-6-15(7-11-17)20(19(23)24,14-4-2-1-3-5-14)16-8-12-18(22)13-9-16/h1-13H,(H2,23,24) | [InChIKey]
SCTZUZTYRMOMKT-UHFFFAOYSA-N | [SMILES]
C(C1C=CC=CC=1)(C1C=CC(F)=CC=1)(C1C=CC(F)=CC=1)C(=O)N |
| Hazard Information | Back Directory | [Description]
Senicapoc is an inhibitor of intermediate conductance calcium-activated potassium (IKCa1/KCa3.1) channels.1,2 It inhibits rubidium efflux from and dehydration of isolated human red blood cells (RBCs) induced by the calcium ionophore A23187 (Item No. 11016; IC50s = 11 and 30 nM, respectively).1 Senicapoc (10 mg/kg twice per day) reduces IKCa1/KCa3.1 channel activity, increases potassium levels in RBCs, and decreases erythrocyte density in the SAD transgenic mouse model of sickle cell disease. It inhibits IL-2, IFN-γ, IL-12, and IL-17A production in CD3+ T cells stimulated with phorbol 12-myristate 13-acetate (PMA; Item No. 10008014) and ionomycin (Item Nos. 10004974 | 11932) when used at a concentration of 1 μM.3 Senicapoc (100 mg/kg) increases the paw withdrawal threshold in a rat model of chronic constriction injury (CCI) of the sciatic nerve.2 | [Uses]
Treatment of disorders mediated by a calcium activated intermediate conductance potassium ion channel antagonist. | [Definition]
Senicapoc (ICA-17043; bis(4-fluorophenyl)phenyl acetamide), a selective, highly potent Gardos channel blocker (IC50 = 11 nM), specifically inhibits the efflux of potassium from the RBCs of both SCD transgenic mice and human sickle cell disease patients. It is derived from clotrimazole-1, a KCNN4 inhibitor. Senicapoc is well tolerated by both healthy volunteers and patients with SCD and has favourable pharmacokinetics, with a long half-life permitting once-daily dosing. It was designed for long-term sickle cell disease therapy to avoid clotrimazole-1 side effects. Whereas Senicapoc is a potent inhibitor of WT KCNN4, its efficiency on mutated channels was unknown[1-2].
| [in vivo]
ICA-17043 (10 mg/kg, p.o.) administration produces a significant decrease in Gardos channel activity measured at day 11 and 21 and is associated with a corresponding increase in red cell K+ content without changes in Na+ content. ICA-17043 (10 mg/kg, twice a day) induces a significant increase in Hct after 11 days of dosing in the SAD mouse[1]. Senicapoc (30 mg/kg, p.o.) reduces airway hyperresponsiveness, eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and vascular remodelling in the sheep[2]. | [storage]
Store at -20°C | [References]
[1] Raphael Rapetti-Mauss. “Senicapoc: a potent candidate for the treatment of a subset of hereditary xerocytosis caused by mutations in the Gardos channel.” Haematologica 101 11 (2016): e431–e435.
[2] Kenneth I Ataga. “Efficacy and safety of the Gardos channel blocker, senicapoc (ICA-17043), in patients with sickle cell anemia.” Blood (2008): 3991–7.
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| Company Name: |
SPIRO PHARMA
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| Telephone: |
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| Website: |
www.spiropharma.com.cn |
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