Phenamil methanesulfonate

Names

[ Name ]:
Phenamil methanesulfonate

[Synonym ]:
2-Pyrazinecarboxamide, 3,5-diamino-N-[(1E)-amino(phenylamino)methylene]-6-chloro-, methanesulfonate (1:1)
Phenaethylphosphorodichloridat
MFCD00274070
2-Cl-IB-MECA
Phenamil methanesulfonate salt
3,5-Diamino-N-[(E)-amino(anilino)methylene]-6-chloro-2-pyrazinecarboxamide methanesulfonate (1:1)
Phosphorodichloridic acid,2-phenylethyl ester
3,5-Diamino-6-chloro-N-(N-phenylcarbamimidoyl)pyrazine-2-carboxamide methanesulfonate (1:1)

Biological Activity

[Description]:

Phenamil methanesulfonate, an analog of Amiloride (HY-B0285), is a more potent and less reversible epithelial sodium channel (ENaC) blocker with an IC50 of 400 nM[2]. Phenamil methanesulfonate is also a competive inhibitor of TRPP3 and inhibits TRPP3-mediated Ca2+ transport with an IC50 of 140 nM in a Ca2+ uptake assay[1]. Phenamil methanesulfonate is an intriguing small molecule to promote bone repair by strongly activating BMP signaling pathway[4]. Phenamil methanesulfonate is used for the research of cystic fibrosis lung disease[5].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Inflammation/Immunology

Research Areas >> Metabolic Disease

[Target]

TRPC3:140 nM (IC50)

[In Vitro]

TRPP3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a Ca2+-activated channel permeable to Ca2+, Na+, and K+. TRPP3 is implicated in regulation of pH-sensitive action potential in spinal cord neurons. Phenamil methanesulfonate (1 μM) decreases 45Ca2+ uptake in a radiotracer uptake assay. It inhibits TRPP3-mediated Ca2+ transport with an IC50 value of 0.28 μM in oocytes expressing TRPP3 or H2O-injected oocytes[1]. Phenamil methanesulfonate is a more potent ENaC blocker than Amiloride, it inhibits the epithelial sodium channel (ENaC) with an IC50 of 400 nM (Amiloride=776 nM)[2]. Phenamil methanesulfonate inhibits basal short-circuit currents with IC50 values of 75 and 116 nM, respectively in both human and ovine bronchial epithelia cells[3]. Phenamil methanesulfonate (0-20 μM; 14 days) elevates adipogenic gene expression, PPARγ, Fabp4, and lipoprotein lipase expression in a concentration-dependent manner ,and regulates adipogenesis in C3H10T1/2 cells[4]. Phenamil methanesulfonate (0-20 μM; 7 or 14 days) modulates MC3T3-E1 osteoblastic differentiation, it increases Alkaline phosphatase (ALP) activity in MC3T3-E1 cells in a concentration-dependent manner[4]. RT-PCR[4] Cell Line: C3H10T1/2 cells Concentration: 0 μM and 20 μM Incubation Time: 14 days Result: Increased PPARγ, Fabp4, and lipoprotein lipase (LPL) mRNA expression.

[In Vivo]

Phenamil methanesulfonate (subcutaneous injection; 15 or 30 mg/kg; 21 days; infusion rate of 1 ml/h) reduces chronic-hypoxia-induced pulmonary artery hypertension (PAH). Additionally, the mRNA level of SMA, SM22, Id3, and Trb3 from the lung sample are also decreased by Phenamil under hypoxia or normoxia in rats. However, phenamil has little effect on pulmonary vasculature under physiological conditions[5]. Animal Model: Male Sprague-Dawley rats[5] Dosage: 15 or 30 mg/kg Administration: Subcutaneous injection; 15 or 30 mg/kg; 21 days; infusion rate of 1 ml/h Result: Reduced hypoxia-induced pulmonary hypertension and vascular remodeling.

[References]

[1]. Xiao-Qing Dai , et al. Inhibition of TRPP3 channel by amiloride and analogs. Mol Pharmacol. . 2007 Dec;72(6):1576-85.

[2]. Andrew J Hirsh, et al.Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis. J Med Chem. 2006 Jul 13;49(14):4098-115.

[3]. Andrew J Hirsh, et al.Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease.J Pharmacol Exp Ther. 2004 Dec;311(3):929-38.

[4]. Mun Chun Chan, et al. The amiloride derivative phenamil attenuates pulmonary vascular remodeling by activating NFAT and the bone morphogenetic protein signaling pathway. Mol Cell Biol

Chemical & Physical Properties

[ Boiling Point ]:
621.7ºC at 760 mmHg

[ Molecular Formula ]:
C₁₃H₁₆ClN₇O₄S

[ Molecular Weight ]:
401.829

[ Flash Point ]:
329.8ºC

[ Exact Mass ]:
401.067291

[ PSA ]:
205.55000

[ LogP ]:
3.38190

[ Vapour Pressure ]:
2.22E-15mmHg at 25°C

[ Storage condition ]:
-20°C

MSDS

Click to get detail MSDS

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2924299090

Customs

[ HS Code ]: 2924299090

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

The lung amiloride-sensitive Na+ channel: biophysical properties, pharmacology, ontogenesis, and molecular cloning.

Proc. Natl. Acad. Sci. U. S. A. 91 , 247, (1994)

Water balance in the lung is controlled via active Na+ and Cl- transport. Electrophysiological measurements on lung epithelial cells demonstrated the presence of a Na+ channel that is inhibited by ami...

Phenamil: an irreversible inhibitor of sodium channels in the toad urinary bladder.

J. Membr. Biol. 87 , 45, (1985)

Several new amiloride analogues and two reported photoaffinity analogues were tested for irreversible inhibition of short-circuit current, Isc, in toad bladder. Bromoamiloride, a photoaffinity analogu...

Biochemical identification of two types of phenamil binding sites associated with amiloride-sensitive Na+ channels.

Biochemistry 28 , 3744, (1989)

The existence of distinct forms of the epithelium Na+ channel that differ in their sensitivity to amiloride has been repeatedly suggested by physiological data. The biochemical basis for these differe...