PIK-75 |
| Catalog No.GC16904 |
PIK-75는 가역적 DNA-PK이고 p110⋱-DNA-PK를 억제하는 선택적 억제제, p110α 및 p110γ IC50은 각각 2, 5.8 및 76nM입니다. PIK-75는 p110α를 억제합니다. p110β보다 200배 이상 강력합니다. (IC50=1.3 μM). PIK-75는 세포 사멸을 유도합니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 372196-77-5
Sample solution is provided at 25 µL, 10mM.
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PIK-75 is a specific inhibitor of p110α isoform of PI3K with IC50 of 5.8 nM [1].
In acute myeloid leukemia cells, PIK-75 targeted the p110α isoform of PI3K, which led to a loss of connection between Bcl-xL and Bak. PIK-75 also transiently decreased Cdk7/9, leading to loss of Mcl-1 protein, and alleviation of its inhibition of pro-apoptotic Bak. The simultaneous loss of Bcl-xL and Mcl-1 led to rapid apoptosis. [2] In human monocyte-endothelial cell, PIK-75 suppressed the events of downstream signaling, including AKT phosphorylation, IKK activation, and NF-kB transcription. PIK-75 inhibited in vitro and in vivo production of TNF-α and IL-6, decreased the E-selectin, ICAM-1, and VCAM-1 expression, and blocked cell adhesion [3]. In human smooth muscle cells, PIK-75 decreased TNF-α-induced CD38 expression in asthmatic and nonasthmatic cells [4]. In pancreatic β-cells, acute treatment with PIK-75 enhanced the glucose-induced insulin secretion [5].
In vivo, PIK-75 significantly suppressed the histological abnormalities associated with dextran sulfate sodium-induced murine colitis. PIK-75 can attenuate experimental inflammation in the colon [3].
References:
[1]. Zheng Z, Amran SI, Thompson PE, Jennings IG. Isoform-selective inhibition of phosphoinositide 3-kinase: identification of a new region of nonconserved amino acids critical for p110α inhibition. Mol Pharmacol. 2011 Oct;80(4):657-64.
[2]. Thomas D, Powell JA, Vergez F, Segal DH, Nguyen NY, Baker A, Teh TC, Barry EF, Sarry JE, Lee EM, Nero TL, Jabbour AM, Pomilio G, Green BD, Manenti S, Glaser SP, Parker MW, Lopez AF, Ekert PG, Lock RB, Huang DC, Nilsson SK, Récher C, Wei AH, Guthridge MA. Targeting acute myeloid leukemia by dual inhibition of PI3K signaling and Cdk9-mediated Mcl-1 transcription. Blood. 2013 Aug 1;122(5):738-48.
[3]. Dagia NM, Agarwal G, Kamath DV, Chetrapal-Kunwar A, Gupte RD, Jadhav MG, Dadarkar SS, Trivedi J, Kulkarni-Almeida AA, Kharas F, Fonseca LC, Kumar S, Bhonde MR. A preferential p110alpha/gamma PI3K inhibitor attenuates experimental inflammation by suppressing the production of proinflammatory mediators in a NF-kappaB-dependent manner. Am J Physiol Cell Physiol. 2010 Apr;298(4):C929-41.
[4]. Jude JA, Tirumurugaan KG, Kang BN, Panettieri RA, Walseth TF, Kannan MS. Regulation of CD38 expression in human airway smooth muscle cells: role of class I phosphatidylinositol 3 kinases. Am J Respir Cell Mol Biol. 2012 Oct;47(4):427-35.
[5]. Aoyagi K, Ohara-Imaizumi M, Nishiwaki C, Nakamichi Y, Ueki K, Kadowaki T, Nagamatsu S. Acute inhibition of PI3K-PDK1-Akt pathway potentiates insulin secretion through upregulation of newcomer granule fusions in pancreatic β-cells. PLoS One. 2012;7(10):e47381.
Kinase experiment: | PI3K enzyme activity is determined in 50 μL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 containing 180 μM phosphatidyl inositol, with the reaction starts by the addition of 100 μM ATP (containing 2.5 μCi of [γ-32P]ATP). After a 30-min incubation at room temperature, the enzyme reaction is stopped by the addition of 50 μL of 1 M HCl. Phospholipids are then extracted with 100 μL of chloroform/methanol [1:1 (v/v)] and 250 μL of 2 M KCl followed by liquid scintillation counting. Inhibitors (e.g., PIK75) ) are diluted in 20% (v/v) DMSO to generate a concentration versus inhibition of enzyme activity curve, which is then analyzed with the use of Prism version 5.00 for Windows to calculate the IC50[2]. |
Cell experiment: | MIA PaCa-2 cells are maintained in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% heat-inactivated fetal bovine serum (HI-FBS), 2.5% horse serum (HS) and 100 U/mL Penicillin/Streptomycin. AsPC-1 cells are cultured in RPMI-1640 media supplemented with 20% HI-FBS, 100 U/mL Penicillin/Streptomycin and 1 mM sodium pyruvate. A total of 2,000 human pancreatic cancer cells (MIA PaCa-2 or AsPC-1) per well are plated in 96-well flat-bottom plates and then treated with either Gemcitabine, PIK-75 alone (0.1 μM, 0.3 μM and 1 μM) or in combination of both drugs with indicated concentrations. At the indicated times, 20 μL of 1 mg/mL MTT in PBS is added to each well and further incubated for ~4 h. After centrifugation and removal of the medium, 150 μL of DMSO is added to each well to dissolve the formazan crystals. The absorbance is measured at 562 nm using an ELx808 absorbance microplate reader. Absorbance of untreated cells is designated as 100%, and the relative viable cells are expressed as a percentage of this value[3] |
Animal experiment: | Mice[3]MIA PaCa-2 cells (~1.7×106 cells/mouse) mixed with Matrigel are injected subcutaneously into the flank of male athymic nude (Foxn1nu) mice aged 6-weeks. Gemcitabine (50 mg/mL) is dissolved in PBS and PIK-75 (20 mg/mL) is dissolved in DMSO. Injection solution is made as 10% of Cremophor EL and 3% of poly(ethylene glycol) 400 in sterile water. Before administration of compounds, Gemcitabine is further diluted in PBS and DMSO or PIK-75 is further diluted in the injection solution and sterilized by 0.2 μm filter unit. These diluents are mixed with 1:1 ratio and administered into peritoneal cavity of the mouse. Gemcitabine (20 mg/kg) or Gemcitabine (20 mg/kg)/PIK-75 (2 mg/kg) combination is administered twice per week and vehicle control and PIK-75 (2 mg/kg) are administered 5 times per week. The body weights and tumor sizes are measured 3 times per week. Tumor volumes are calculated. |
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. | |
| Cas No. | 372196-77-5 | SDF | |
| Chemical Name | N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide;hydrochloride | ||
| Canonical SMILES | CC1=C(C=C(C=C1)[N+](=O)[O-])S(=O)(=O)N(C)N=CC2=CN=C3N2C=C(C=C3)Br.Cl | ||
| Formula | C16H14BrN5O4S.HCl | M.Wt | 488.74 |
| Solubility | ≥ 8.15mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.0461 mL | 10.2304 mL | 20.4608 mL |
| 5 mM | 409.2 μL | 2.0461 mL | 4.0922 mL |
| 10 mM | 204.6 μL | 1.023 mL | 2.0461 mL |
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- Purity: >99.50%
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Average Rating: 5 (Based on Reviews and 10 reference(s) in Google Scholar.)
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