PIK-93

Catalog No.S1489 Batch:S148901

Technical Data

Formula

C₁₄H₁₆ClN₃O₄S₂

Molecular Weight

389.88

CAS No.

593960-11-3

Solubility (25°C)*

In vitro

DMSO

78 mg/mL (200.06 mM)

Ethanol

1 mg/mL (2.56 mM)

Water

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

30%PEG400 1 0.5%Tween80 2 5%propylene glycol

30.0mg/ml

Taking the 1 mL working solution as an example, add 300 μL of 100 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O to adjust the volume. to 1 mL. The mixed solution should be used immediately for optimal results.

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

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.

Targets

p110γ ^[1]	PI4KIIIβ ^[1]	p110α ^[1]	DNA-PK ^[1]	p110δ ^[1]	View More
16 nM	19 nM	39 nM	64 nM	120 nM	View More

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. ^[1] 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. ^[2] 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. ^[3] In T6.11 cells, PIK-93 (300 nM) reduces carbachol-induced translocation of TRPC6 to the plasma membrane and net Ca²⁺ entry. ^[4] 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. ^[5]

Features

A novel and potent inhibitor of both PI3Kγ and PI4KIIIβ.

Protocol (from reference)

Kinase Assay:^{^[1]}	Assay of PI3Ks IC50 values are measured using a standard TLC assay for lipid kinase activity. Kinase reactions are performed by preparing areaction mixture containing kinase, PIK-93 (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl₂), and freshly sonicated phosphatidylinositol (100 µg/ml). Reactions are initiated by the addition of ATP containing 10 µCi of γ-³²P-ATP to a final concentration 10 or 100 µM, and allowed to proceed for 20 min at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 µL 1N HCl followed by 160 µL CHCl₃:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase transferred to a new tube using a gel loading pipette tip precoated with CHCl₃. This extract is spotted on TLC plates and developed for 3 hours–4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen, and quantitated. Kinase activity is typically measured at 10–12 concentrations of PIK-93 representing two-fold dilutions from the highest concentration of 100 μM.
Cell Assay:^{^[2]}	Cell lines Differentiated HL60 (dHL60) cells Concentrations 0.5 μM–1 μM Incubation Time 40 min Method For actin staining, dHL60 cells are preincubated in suspension with PIK-93 or vehicle for 40 min, centrifuged for 5 min at 2000 rpm at room temperature in a J6-B centrifuge, resuspended in mHBSS containing the respective agent at the same concentration, allowed to stick to fibronectin-covered coverslips, and subjected to stimulation with a uniform concentration of 100 nM f-Met-Leu-Phe (fMLP) for 3 min. Cellsare fixed in 3.7% PFA and stained with 10 units/mL rhodamine-phalloidin for 15 min.

Kinase Assay:^{^[1]}

Assay of PI3Ks
IC50 values are measured using a standard TLC assay for lipid kinase activity. Kinase reactions are performed by preparing areaction mixture containing kinase, PIK-93 (2% DMSO final concentration), buffer (25 mM HEPES, pH 7.4, 10 mM MgCl₂), and freshly sonicated phosphatidylinositol (100 µg/ml). Reactions are initiated by the addition of ATP containing 10 µCi of γ-³²P-ATP to a final concentration 10 or 100 µM, and allowed to proceed for 20 min at room temperature. For TLC analysis, reactions are then terminated by the addition of 105 µL 1N HCl followed by 160 µL CHCl₃:MeOH (1:1). The biphasic mixture is vortexed, briefly centrifuged, and the organic phase transferred to a new tube using a gel loading pipette tip precoated with CHCl₃. This extract is spotted on TLC plates and developed for 3 hours–4 hours in a 65:35 solution of n-propanol:1M acetic acid. The TLC plates are then dried, exposed to a phosphorimager screen, and quantitated. Kinase activity is typically measured at 10–12 concentrations of PIK-93 representing two-fold dilutions from the highest concentration of 100 μM.

Cell Assay:^{^[2]}

Cell lines
Differentiated HL60 (dHL60) cells
Concentrations
0.5 μM–1 μM
Incubation Time
40 min
Method
For actin staining, dHL60 cells are preincubated in suspension with PIK-93 or vehicle for 40 min, centrifuged for 5 min at 2000 rpm at room temperature in a J6-B centrifuge, resuspended in mHBSS containing the respective agent at the same concentration, allowed to stick to fibronectin-covered coverslips, and subjected to stimulation with a uniform concentration of 100 nM f-Met-Leu-Phe (fMLP) for 3 min. Cellsare fixed in 3.7% PFA and stained with 10 units/mL rhodamine-phalloidin for 15 min.

References

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Customer Product Validation

: , , Dr. Zhang of Tianjin Medical University

Selleck's PIK-93 has been cited by 11 publications

Golgi retention and oncogenic KIT signaling via PLCγ2-PKD2-PI4KIIIβ activation in gastrointestinal stromal tumor cells [ Cell Rep, 2023, 42(9):113035]	PubMed: 37616163
Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity [ ACS Chem Biol, 2022, 10.1021/acschembio.2c00052]	PubMed: 35439415
ACBD3 modulates KDEL receptor interaction with PKA for its trafficking via tubulovesicular carrier [ BMC Biol, 2021, 19(1):194]	PubMed: 34493279
The carboxy terminal coiled-coil modulates Orai1 internalization during meiosis [ Sci Rep, 2021, 11(1):2290]	PubMed: 33504898
The carboxy terminal coiled-coil modulates Orai1 internalization during meiosis [ Sci Rep, 2021, 11(1):2290]	PubMed: 33504898
Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation [ J Immunol, 2021, 206(9):2061-2074]	PubMed: 33827893
Escherichia coli as a platform for the study of phosphoinositide biology. [ Sci Adv, 2019, 5(3):eaat4872]	PubMed: 30944849
A Single Point Mutation in the Rhinovirus 2B Protein Reduces the Requirement for Phosphatidylinositol 4-Kinase Class III Beta in Viral Replication [ J Virol, 2018, 92(23)e01462-18]	PubMed: 30209171
Streptococcus pneumoniae Induces Autophagy through the Inhibition of the PI3K-I/Akt/mTOR Pathway and ROS Hypergeneration in A549 Cells. [Li P, et al. PLoS One, 2015, 10(3):e0122753]	PubMed: 25803050
Functional kinomics identifies candidate therapeutic targets in head and neck cancer. [ Clin Cancer Res, 2014, 20(16):4274-88]	PubMed: 25125259

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