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SML2635

Sigma-Aldrich

Z944 hydrochloride

≥98% (HPLC)

Synonym(s):

4-[[(3-Chloro-5-fluorobenzoyl)amino]methyl]-N-(1,1-dimethylethyl)-1-piperidineacetamide hydrochloride, N-((1-(2-(tert-Butylamino)-2-oxoethyl)piperidin-4-yl)methyl)-3-chloro-5-fluorobenzamide hydrochloride, Z 944 hydrochloride, Z-944

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About This Item

Empirical Formula (Hill Notation):
C19H27ClFN3O2 · xHCl
Molecular Weight:
383.89 (free base basis)
UNSPSC Code:
12352200
NACRES:
NA.77
Pricing and availability is not currently available.

Assay

≥98% (HPLC)

form

powder

storage condition

desiccated

color

white to beige

solubility

H2O: 2 mg/mL, clear

storage temp.

2-8°C

Biochem/physiol Actions

Orally available, state-dependent, potent and selective T-type calcium channel blocker (Cav3.1, Cav3.2, Cav3.3) with in vivo absence seizure-reducing efficacy.
Z944 is an orally available, state-dependent, potent and selective T-type calcium channel blocker (hCav3.1/Cav3.2/Cav3.3 IC50 by voltage clamp = 50/160/110 nM under ~30% inactivated state & 130/540/260 nM in the closed state) over non-T-type voltage-gated channels (rCaV2.2 IC50 = 11 μM/30% inactivated & 150 μM/closed; hERG/rCaV1.2/hNaV1.5 IC50 = 7.8/32/100 μM). Z944 effectively suppresses seizure activity in the GAERS (absence epilepsy rats from Strasbourg) model in vivo (10-30 mg/kg qod ip.) with no adverse cardiovascular effects or neurotoxicity.

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

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Certificates of Analysis (COA)

Lot/Batch Number
0000194242
0000187050

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Z944: a first in class T-type calcium channel modulator for the treatment of pain.
M Lee
Journal of the peripheral nervous system : JPNS, 19 Suppl 2, S11-S12 (2014-10-02)
Wendie N Marks et al.
Neuroscience, 332, 121-129 (2016-07-02)
The role of T-type calcium channels in brain diseases such as absence epilepsy and neuropathic pain has been studied extensively. However, less is known regarding the involvement of T-type channels in cognition and behavior. Prepulse inhibition (PPI) is a measure
Wendie N Marks et al.
Neurobiology of disease, 94, 106-115 (2016-06-11)
Childhood absence epilepsy (CAE) is often comorbid with behavioral and cognitive symptoms, including impaired visual memory. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is an animal model closely resembling CAE; however, cognition in GAERS is poorly understood. Crossmodal object recognition
Elizabeth Tringham et al.
Science translational medicine, 4(121), 121ra19-121ra19 (2012-02-22)
Absence seizures are a common seizure type in children with genetic generalized epilepsy and are characterized by a temporary loss of awareness, arrest of physical activity, and accompanying spike-and-wave discharges on an electroencephalogram. They arise from abnormal, hypersynchronous neuronal firing
Wendie N Marks et al.
Learning & memory (Cold Spring Harbor, N.Y.), 25(7), 317-324 (2018-06-17)
The roles of low-voltage-activated (T-type) calcium channels in brain diseases have been studied extensively. Less is known regarding the involvement of T-type channels in cognition and behavior. Sensory integration (SI) is a cognitive process whereby the brain uses unimodal or
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