3,4,5-Trimethoxy-N-(2-methoxyethyl)-N-(4-phenyl-2-thiazolyl)-benzamide

3,4,5-Trimethoxy-N-(2-methoxyethyl)-N-(4-phenyl-2-thiazolyl)-benzamide Property

Boiling point:

595.9±60.0 °C(Predicted)

Density 

1.237±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: soluble20mg/mL, clear

pka

2.27±0.10(Predicted)

form 

powder

color 

white to beige

Safety

Hazard Codes 

Xn

Risk Statements 

22

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H317May cause an allergic skin reaction

H319Causes serious eye irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

3,4,5-Trimethoxy-N-(2-methoxyethyl)-N-(4-phenyl-2-thiazolyl)-benzamide Chemical Properties,Usage,Production

Description

Eact is an activator of the calcium-activated chloride channel anoctamin 1 (ANO1). It increases chloride currents in FRT cells expressing human ANO1 (EC₅₀ = 3 μM). It is selective for ANO1 over cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels and epithelial sodium channels (ENaCs) in FRT cells at 10 μM. Eact (20 μM) increases the rate of submucosal gland fluid secretion in human bronchi isolated from patients with cystic fibrosis and healthy individuals. It increases production of mitochondrial reactive oxygen species (ROS), reduces the mitochondrial membrane potential, and induces apoptosis in rat lung microvascular endothelial cells (RLMVECs), as well as reduces total cell counts in pulmonary artery endothelial cell populations isolated from patients with idiopathic pulmonary arterial hypertension (IPAH). Eact also activates transient receptor potential vanilloid 1 (TRPV1) in HEK293T cells expressing the mouse receptor (EC₅₀ = 11.6 μM) and induces scratching and licking behaviors in wild-type, but not Trpv1^-/-, mice.

Uses

Eact is a Ca2+ activated chloride channel protein, which may be used for the treatment of diseases and disorders involving this particular channel such as cystic fibrosis, disorders related to salivary gland dysfunction, dry eye syndrome and intestinal hypomotility.

Biochem/physiol Actions

Eact activates the Calcium-activated Chloride channel (CaCC) TMEM16A CaCC. Eact stimulates CaCC conductance in salivary gland cells and submucosal airway epithelial cells. The compound Eact also stimulates submucosal gland secretion in human bronchial tissue and smooth muscle contraction in mouse intestine.

storage

Store at +4°C

References

[1] WAN NAMKUNG. Small-molecule activators of TMEM16A, a calcium-activated chloride channel, stimulate epithelial chloride secretion and intestinal contraction[J]. FASEB Journal, 2011, 25 11: 4048-4062. DOI: 10.1096/fj.11-191627
[2] AYED M ALLAWZI. Activation of Anoctamin-1 Limits Pulmonary Endothelial Cell Proliferation via p38-Mitogen-activated Protein Kinase-Dependent Apoptosis.[J]. American Journal of Respiratory Cell and Molecular Biology, 2018, 58 5: 658-667. DOI: 10.1165/rcmb.2016-0344oc
[3] SHENBIN LIU. Eact, a small molecule activator of TMEM16A, activates TRPV1 and elicits pain‐ and itch‐related behaviours[J]. British Journal of Pharmacology, 2016, 173 1: 1208-1218. DOI: 10.1111/bph.13420