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Home / Biochemicals / Small Molecules

SKA-121

SKU : BHB21300331

A Selective Positive Gating Modulator of KCa3.1 Channels

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Alomone Labs

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Mfr.No.	S-245, S-245_10 mg, S-245_25 mg, S-245_5 mg, S-245_50 mg
Description	SKA-121 (#S-245) is a highly pure, synthetic, and biologically active compound.
Molecular Formula	C12H10N2O
Synonyms	Synthetic
Background	KCa3.1 is a calcium-activated K+ channel. KCa2/3 channels are voltage-independent and share a Ca2+/calmodulin-mediated gating mechanism1.KCa3.1 and KCa2 channels are expressed in cells and enable them to hyperpolarize in order to regulate Ca2+ influx through inward rectifier Ca2+ channels, pass on hyperpolarization through gap junctions, or regulate firing frequency by preventing an untimely or premature action potential initiation2. Pharmacological activation of KCa channels has therefore been suggested as a treatment for various diseases. The different specific activities of KCa2 and KCa3.1 channels create a difference between the activators of these two types of channels. KCa2 activators can potentially reduce neuronal excitability in central nervous system disorders like epilepsy and ataxia. KCa3.1 activators could be useful as endothelial targeted antihypertensives and to enhance fluid secretion in the airways in cystic fibrosis3,4.The positive-gating modulators used until today have low selectivity and affect both KCa2 and KCa3.1, making it impossible to differentiate the phenotypes of these two receptors. To avoid KCa2 channel-mediated side effects, it is highly desirable to identify selective KCa3.1 activators that could be used as pharmacological tools to further dissect the in vivo role of KCa3.1 in blood pressure control and to help determine whether KCa3.1 activators could eventually be developed into a new class of endothelial-targeted antihypertensives. SKA-121 (5-methylnaphtho(2,1-d)oxazol-2-amine), a compound generated through an isosteric replacement approach, activates KCa3.1 with an EC50 of 111 nM, exhibits 40- to 80-fold selectivity over the three KCa2 channels and lowers blood pressure in mice as determined by telemetry without exerting KCa2 channel-mediated effects on HR5.
Shipping	Shipped at room temperature. Product as supplied can be stored intact at room temperature for several weeks. For longer periods, it should be stored at -20°C
Concentration	100 nM - 10 uM
Reconstitution	Soluble in DMSO. Spin down all products before handling.
Cas Number	1820708-73-3
Molecular Weight	198.22
Solubility	Soluble in DMSO. Spin down all products before handling.
Target	KCa3.1 channels
Activity	SKA-121 is a positive gating modulator of KCa3.1 channels (EC50 of 109 nM), potent and selective over KCa2 subtypes (EC50 of 4.4-8.7 uM). Significantly lowers mean arterial blood pressure in vivo in wild-type hypertensive mice (100 mg/kg i.p.)1.
Country Of Origin	Israel/IL
UNSPSC Code	41116134
Application	FC- Flow cytometry, IFC- Indirect flow cytometry, IHC- Immunohistochemistry,LCI- Live cell imaging, Calcium imaging assay,Cell survival assay, Electrophysiology, Neurite outgrowth assay
Lead Time	1-2 Business Days
Notes	Bioassay Tested: Yes Chemical Name: 5-methylbenzo(g)(1,3)benzoxazol-2-amine

Purity	>97% (HPLC)
Form	Powder
Storage	Storage After Reconstitution: The reconstituted solution can be stored at 4°C for up to 1 week. For longer periods (up to 6 months), small aliquots should be stored at -20°C. We do not recommend storing the product in working solutions for longer than a few days. Avoid multiple freeze-thaw cycles. Storage of solutions: Store at -20°C. It is recommended to aliquot stock solutions to avoid repeated thawing and freezing.

Product Manual	SDS

Reference	Fanger, C.M. et al. (1999) J. Biol. Chem. 274, 5746. Adelman, J.P. et al. (2012) Annu. Rev. Physiol. 74, 245. Wulff, H and Kohler, R. (2013) J. Cardiovasc. Pharmacol. 61, 102. Wulff, H. and Zhorov, B.S. (2008) Chem. Rev. 108, 1744. Coleman, N. et al. (2014) Mol. Pharmacol. 86, 342. Coleman, N. et al. (2014) Mol. Pharmacol. 86, 342.

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Combination SKU	Supplier No.	Size	Your price	Quantity
BHB21300331-1	S-245_10 mg	10 mg	$235		Add to Cart
BHB21300331-2	S-245_25 mg	25 mg	$469		Add to Cart
BHB21300331-3	S-245_5 mg	5 mg	$134		Add to Cart
BHB21300331-4	S-245_50 mg	50 mg	$747		Add to Cart

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