PIK-93
(Synonyms: N-[5-[4-氯-3-[[(2-羟基乙基)氨基]磺酰基]苯基]-4-甲基-2-噻唑基]乙酰胺) 目录号 : GC13089
A PI4KIIIβ inhibitor
Cas No.:593960-11-3
Sample solution is provided at 25 µL, 10mM.
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PIK-93 is a potent and novel inhibitor of p110γ (PI3Kγ) and PI4KIIIβ (IC50= 16 nM and 19 nM, respectively).
PI3K (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. It plays a key role in PI3K/Akt/mTOR pathway.
Inhibition of PI3K via PIK-93 reduced the carbachol-activated translocation of TRPC6 to the plasma membrane and carbachol-activated net Ca(2+) entry into T6.11 cells. [1] PIK-93 also selectively inhibited the PI4KIIIβ enzyme, and siRNA-mediated down regulation of individual PI4-enzymes in COS-7 cells. [2] Furthermore, as a potent anti-PV compound, PIK93 targeted PI4Kβ to inhibit interaction of viral 3D polymerase and phosphatidylinositol 4-phosphate on the reorganized membrane vesicle for viral replication complex formation. [3] PIK93 also showed anti-PV with an EC50 of 0.14 μM for PV pseudovirus infection. [4]
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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Kinase experiment: |
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. |
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Cell experiment: |
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. Cells are fixed in 3.7% PFA and stained with 10 units/mL rhodamine-phalloidin for 15 min. |
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References: [1]. Knight ZA, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006 May 19;125(4):733-47 |
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| Cas No. | 593960-11-3 | SDF | |
| 别名 | N-[5-[4-氯-3-[[(2-羟基乙基)氨基]磺酰基]苯基]-4-甲基-2-噻唑基]乙酰胺 | ||
| 化学名 | N-[5-[4-chloro-3-(2-hydroxyethylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide | ||
| Canonical SMILES | CC1=C(SC(=N1)NC(=O)C)C2=CC(=C(C=C2)Cl)S(=O)(=O)NCCO | ||
| 分子式 | C14H16ClN3O4S2 | 分子量 | 389.88 |
| 溶解度 | ≥ 19.5mg/mL in DMSO, ≥ 2.33 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5649 mL | 12.8245 mL | 25.6489 mL |
| 5 mM | 0.513 mL | 2.5649 mL | 5.1298 mL |
| 10 mM | 0.2565 mL | 1.2824 mL | 2.5649 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet