

Supplier:
Alomone Labs Limited.Cat no: D-100
BUY Dofetilide
The KV11.1 (HERG) channel is a member of the ether-a-go-go (EAG) subfamily of voltage-dependent K+ channels that includes the related proteins KV11.2 and KV11.3 (erg2 and erg3). The KV11.1 current is characterized by strong inward rectification with slow activation and very rapid inactivation kinetics.
The channel is expressed in the brain and heart (where it underlies the IKr current) and has a central role in mediating repolarization of action potentials.
Mutations in the KV11.1 channel cause inherited long QT syndrome (LQTS) or abnormalities in the repolarization of the heart that are associated with life-threatening arrhythmias and sudden death. All the identified KV11.1 mutations produce loss of function of the channel via several cellular mechanisms ranging from alterations of gating properties, channel permeability/selectivity andпїЅintracellular channel trafficking that decreases the number of channels that reach the cell membrane.
Lately, drug-induced forms of LQTS have been reported for a wide range of non-cardiac drugs including antihistamines, psychoactive agents and antimicrobials. All these drugs potently block the KV11.1 channel as an unintended side effect, prompting regulatory drug agencies to issue recommendations for the testing of new drugs for their potential KV11.1 blocking effect.
In addition, KV11.1 expression was found to be upregulated in several tumor cell lines of different histogenesis suggesting that it confers the cells some advantage in cell proliferation. Indeed, in several studies it has been shown that inhibition of the KV11.1 current leads to a decrease in tumor cell proliferation.
Dofetilite is a class II antiarrythmic agent which blocks the fast delayed rectifier cardiac K+ current, mostly carried out by KV11.1 (hERG) channels. In mouse atrial tumor myocytes (AT-1 cells), dofetilide was very effective in inhibiting the IKr current with IC50 of 12 nM.
Dofetilide was effective in inhibiting KV11.1 channels in Xenopus oocytes with 1 μM, thereby eliminating the current. 500 nM Dofetilide enhanced smooth muscle from bovine epididymal duct contractions as expected by blocking KV11.1 channels in this preparation.
Ion Channel Modulators; K+ Channel Blockers.
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SPECIFICATIONS
Catalog Number
D-100
Size
25 mg
Purity
>98%
Concentration
0.5 uM - 100 uM
Shipping Temp
Room Temperature
Molecular Weight
441.6 da
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