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SAK3

Cat. No. M8772
SAK3 Structure
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Biological Activity

SAK3 is a potent and orally active spiroimidazopyridine derivative that enhances Cav3.1 and Cav3.3, but not Cav3.2, T-type voltage-gated Ca2+ channel (T-VGCC) activity (∼20% peak current increase with 0.1 nM SAK3 by whole-cell patch-clamp using human Cav3.1 or Cav3.3 transfected neuro2A; no effect up to 10 nM using Cav3.2 transfectant). Acute SAK3 oral administration (0.5 mg/kg) significantly enhances hippocampal CA1 region acetylcholine (ACh) release in naïve mice, as well as increases hippocampal ACh levels and improves memory deficits among olfactory-bulbectomized (OBX) mice. Daily SAK3 oral administration 24 hrs following hypothyroidism induction by methimazole (MMI) is efficacious against MMI-induced medial septum (MS) cholinergic neurons loss (0.5-1 mg/kg/day) and cognitive deficits (1 mg/kg/day).

Chemical Information
Molecular Weight 369.41
Formula C20H23N3O4
CAS Number 1256269-87-0
Solubility (25°C) DMSO: 2 mg/mL
Storage Powder          -20°C   3 years ;  4°C   2 years
In solvent       -80°C   6 months ;  -20°C   1 month
Conversion of different model animals based on BSA (PMID: 27057123)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 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 Compound A of 10 mg/kg.

References

[1] Chinnasamy Dhanalakshmi, et al. Evaluation of the effects of the T-type calcium channel enhancer SAK3 in a rat model of TAF1 deficiency

[2] Hisanao Izumi, et al. SAK3 Administration Improves Spine Abnormalities and Cognitive Deficits in App NL-G-F/NL-G-F Knock-in Mice by Increasing Proteasome Activity through CaMKII/Rpt6 Signaling

[3] Nopparat Suthprasertporn, et al. Neuroprotection of SAK3 on scopolamine-induced cholinergic dysfunction in human neuroblastoma SH-SY5Y cells

[4] Kohji Fukunaga, et al. SAK3-Induced Neuroprotection Is Mediated by Nicotinic Acetylcholine Receptors

[5] Kohji Fukunaga, et al. Alzheimer's disease therapeutic candidate SAK3 is an enhancer of T-type calcium channels

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