PIK-93 is the first potent, synthetic PI4K (PI4KIIIβ) inhibitor with IC50 of 19 nM, and also inhibits PI3Kγ and PI3Kα with IC50 of 16 nM and 39 nM, respectively.
IC50&Target
p110α
39 nM (IC50)
p110β
590 nM (IC50)
p110δ
120 nM (IC50)
p110γ
16 nM (IC50)
PI3KC2α
16 μM (IC50)
PI3KC2β
140 nM (IC50)
PI4KIIIβ
19 nM (IC50)
PI4KIIIα
1.1 μM (IC50)
hsVPS34
320 nM (IC50)
DNA-PK
64 nM (IC50)
ATM
490 nM (IC50)
mTORC1
1.38 μM (IC50)
ATR
17 μM (IC50)
体外研究
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 [H]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 Ca 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.
分子式
C14H16N3O4S2Cl
分子量
389.88
CAS号
593960-11-3
运输条件
Room temperature in continental US; may vary elsewhere.