Retigabine (Ezogabine, D-23129) is an anticonvulsant for KCNQ2/3 currents with EC50 of 3.6 μM. Retigabine is a KCNQ/Kv7 potassium channel activator which functions by enhancing potassium currents via stabilizing the open conformation of the Kv7.2-7.3 channels. Studies indicate that the agonist binds in between two subunits of the channel which allows it to stabilize the channels open conformation. In addition, KCNQ3, a type of KCNQ channel, includes a hydrophobic pocket which contains a Leu338 region which is the binding site for retigabine. Furthermore, Retigabine has been shown to accelerate the activation of neuronal resting potentials while slowing deactivation of these currents. Secondly, Retigabine selectively activates the KCNQ2-5 isoforms, which results in an increased open channel probability. Studies also indicate that this compound can act as a GABA enhancer via amplifying the production of GABA in cortical neurons.
|Cell lines||MDA-MB-231 and MDA-MB-435 cells|
|Preparation method||Inhibition of DNA synthesis assay. MDA-MB-231 and MDA-MB-435 cells were placed in 6-well culturedishes at 10,000 cells/well in 2 ml of medium. The following day, 5-AZA-CdR and depsi, alone or in combination, were added to thecells at the indicated concentrations. At 48 hr, 0.5μ Ci [3H]thymidine (6.7 Ci/mmol, ICN Biomedicals, Irvine, CA) was addedto the medium for an additional 24 hr. The cells were then rinsedwith PBS, trypsinized, suspended in a 0.9% NaCl solution, trans-ferred to a 25 mm diameter GF/C glass ﬁber ﬁlter and washed withcold 0.9% NaCl, 5% trichloroacetic acid and ethanol solutions.The dried ﬁlters were placed in EcoLite scintillation ﬂuid (ICNBiomedicals) and the radioactivity incorporated into DNA wasmeasured with a scintillation counter.|
|Incubation time||24 hr|
|Animal models||EJ6 human bladder cancer cell tumor-bearing athymic nu/nu mice|
|Dosages||5 mg/kg every 7 days for 25 days|
|Administration||subcutaneous (SQ) administration|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 30 mg/mL|
S110, a 5-Aza-2'-deoxycytidine-containing dinucleotide, is an effective DNA methylation inhibitor in vivo and can reduce tumor growth.
Chuang JC, et al. Mol Cancer Ther. 2010 May;9(5):1443-50. PMID: 20442312.
Synergistic antineoplastic action of DNA methylation inhibitor 5-AZA-2'-deoxycytidine and histone deacetylase inhibitor depsipeptide on human breast carcinoma cells.
Primeau M, et al. Int J Cancer. 2003 Jan 10;103(2):177-84. PMID: 12455031.
|Related Potassium Channel Products|
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ML213 (CID-3111211) is a selective KV7.2 (KCNQ2) and KV7.4 (KCNQ4) channel opener, with EC50 values of 230 and 510 nM for KV7.2 and KV7.4, respectively.
CLP290 is a novel, orally available KCC2 modulator, highly selective for KCC2 over related Cl- transporters.
BMS-191011 is a potent BKCa channel opener (large-conductance Ca2+-activated potassium channel, KCa1.1).
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