593960-11-3 Usage
Description
N-[5-[4-Chloro-3-[[(2-hydroxyethyl)amino]sulfonyl]phenyl]-4-methyl-2-thiazolyl]acetamide, also known as PIK-93, is a potent and synthetic inhibitor of phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ) with an IC50 of 19 nM. It selectively inhibits PI4KIIIβ over other PI4K isoforms and also inhibits the PI3K catalytic subunits. PIK-93 has been shown to reduce enteroviral RNA replication and inhibit the transport of ceramide from the endoplasmic reticulum to the Golgi apparatus.
Uses
Used in Pharmaceutical Industry:
PIK-93 is used as a PI3Kγ and PI4KIIIβ inhibitor for the development of drugs targeting these enzymes. Its ability to inhibit these enzymes makes it a potential candidate for the treatment of various diseases, including cancer and viral infections.
Used in Virology Research:
PIK-93 is used as a research tool to study the role of PI4KIIIβ and PI3K in enteroviral RNA replication. Its ability to reduce enteroviral RNA replication in HeLa cells makes it a valuable compound for understanding the mechanisms of viral replication and the development of antiviral therapies.
Used in Cell Biology Research:
PIK-93 is used as a research tool to investigate the role of PI4KIIIβ and PI3K in the transport of ceramide from the endoplasmic reticulum to the Golgi apparatus. Its ability to inhibit this transport process makes it a useful compound for studying the regulation of lipid trafficking and its implications in cellular function and disease.
Features
A novel and potent inhibitor of both PI3Kγ and PI4KIIIβ.
In vitro
PIK-93 inhibits PI3Kγ and PI4KIIIβ, with IC50 values of 16 nM and 19 nM, respectively. PIK-93 also inhibits other members of PI3Ks, including PI3Kα, β, and δ, with IC50 values of 39 nM, 0.59 μM, and 0.12 μM, respectively. PIK-93 shows no obvious inhibitory effect against a panel of other kinases, even at a concentration of 10 μM. In differentiated HL60 (dHL60) cells, PIK-93 (0.5 μM–1 μM) impairs consolidation and stability of the leading edge formed after treatment with uniform f-Met-Leu-Phe (fMLP). PIK-93 alters the localization, but not the amount, of the fMLP-dependent accumulation of total F-actin. In fMLP gradients, PIK-93 reduces the chemotactic index and triples the cells' turning frequency. In COS-7 cells, PIK-93 (250 nM) effectively abrogates the accumulation of CERT-PH domain and FL-Cer in Golgi. PIK-93 of the same concentration also significantly inhibits the conversion of [3H]serine-labeled endogenous ceramide to sphingomyelin. These facts indicate a key role of PI4KIIIβ in ceramide transport between the ER and Golgi, as well as in the regulation of spingomyelin synthesis. In T6.11 cells, PIK-93 (300 nM) reduces carbachol-induced translocation of TRPC6 to the plasma membrane and net Ca2+ entry. A recent report shows that PIK-93 has anti-enterovirus effects, as revealed by its inhibition of both poliovirus (PV) and hepatitis C virus (HCV) replication, with EC50 values of 0.14 μM and 1.9 μM, respectively.
Enzyme inhibitor
This potent and selective PI3Kγ/PI4KIIIβ inhibitor (FW = 389.88; CAS 593960-11-3; Solubility (25°C): 78 mg/mL DMSO, <1 mg/mL Water), also known as N-[5-[4-chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4- methylthiazol-2-yl]acetamide, impairs actin filament consolidation and stability at the leading edge in cells treated with N-formyl-Met-Leu-Phe as well as ceramide transport between ER and Golgi compartments. The inhibition of PI3K by PIK-93, LY294002, or wortmannin decreased carbachol-induced translocation of TRPC6 to the plasma membrane and carbachol-induced net Ca2+ entry into T6.11 cells. PIK-93 inhibits both poliovirus (PV) and hepatitis C virus (HCV) replication, with EC50 values of 0.14 μM and 1.9 μM, respectively. Targets: PI3Kγ, IC50 = 16 nM; PI4KIIIβ, IC50 = 19 nM; PI3Kα, IC50 = 39 nM; PI3Kδ, IC50 = 0.12 μM; and PI3Kβ, IC50 = 0.59 μM.
references
[1] monet m, francoeur n, boulay g. involvement of phosphoinositide 3-kinase and pten protein in mechanism of activation of trpc6 protein in vascular smooth muscle cells. j biol chem. 2012 may 18;287(21):17672-81.[2] tóth b, balla a, ma h et al. phosphatidylinositol 4-kinase iiibeta regulates the transport of ceramide between the endoplasmic reticulum and golgi. j biol chem. 2006 nov 24;281(47):36369-77.[3] hsu, n. y., et al. 2010. viral reorganization of the secretory pathway generates distinct organelles for rna replication. cell 141:799-811.[4] arita m, kojima h, nagano t et al. phosphatidylinositol 4-kinase iii beta is a target of enviroxime-like compounds for antipoliovirus activity. j virol. 2011 mar;85(5):2364-72.
Check Digit Verification of cas no
The CAS Registry Mumber 593960-11-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 5,9,3,9,6 and 0 respectively; the second part has 2 digits, 1 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 593960-11:
(8*5)+(7*9)+(6*3)+(5*9)+(4*6)+(3*0)+(2*1)+(1*1)=193
193 % 10 = 3
So 593960-11-3 is a valid CAS Registry Number.
