| Identification | Back Directory | [Name]
N-[5-[4-Chloro-3-[[(2-hydroxyethyl)amino]sulfonyl]phenyl]-4-methyl-2-thiazolyl]acetamide | [CAS]
593960-11-3 | [Synonyms]
PI-93
PIK 93
PIK-93,PIK93
PI 3,4-K inhibitor, PIK-93
N-[5-[4-Chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl]-4-methylthiazol-2-yl]acetamide
N-(5-(4-Chloro-3-(N-(2-hydroxyethyl)sulfamoyl)phenyl)-4-methylthiazol-2-yl)acetamide
N-[5-[4-Chloro-3-[[(2-hydroxyethyl)amino]sulfonyl]phenyl]-4-methyl-2-thiazolyl]acetamide
AcetaMide, N-[5-[4-chloro-3-[[(2-hydroxyethyl)aMino]sulfonyl]phenyl]-4-Methyl-2-thiazolyl]-
PIK 93
N-[5-[4-Chloro-3-[[(2-hydroxyethyl)amino]sulfonyl]phenyl]-4-methyl-2-thiazolyl]acetamide
N-[5-[4-Chloro-3-[[(2-hydroxyethyl)amino]sulfonyl]phenyl]-4-methyl-2-thiazolyl]acetamide PIK 93 | [Molecular Formula]
C14H16ClN3O4S2 | [MDL Number]
MFCD12922510 | [MOL File]
593960-11-3.mol | [Molecular Weight]
389.88 |
| Questions And Answer | Back Directory | [Description]
PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC50 of 19 nM; shown to inhibit PI3Kα with IC50 of 39 nM. | [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. |
| Hazard Information | Back Directory | [Uses]
PIK 93 is a PI3Kγ and PI4KIIIβ inhibitor. | [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. | [target]
PI3Kγ | [IC 50]
PI4KIIIβ: 19 nM (IC50); PI4KIIIα: 1.1 μM (IC50); p110γ: 16 nM (IC50); p110α: 39 nM (IC50); p110δ: 120 nM (IC50); p110β: 590 nM (IC50); PI3KC2β: 140 nM (IC50); PI3KC2α: 16 μM (IC50); hsVPS34: 320 nM (IC50); DNA-PK: 64 nM (IC50); ATM: 490 nM (IC50); mTORC1: 1.38 μM (IC50); ATR: 17 μM (IC50) | [storage]
Store at -20°C | [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. |
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