Antibodies
SGI-1776 free base
- 貨號 Cat. No.
- S2198
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
SGI-1776 free base
SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | SGI-1776 is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin. Phase 1. | |||||
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| Targets | Pim1 | Pim2 | Pim3 | FLT3 | ||
| IC50 | 7 nM | 363 nM | 69 nM | 44nM [1] | ||
| In vitro | In addition to Pim, SGI-1776 also potently targets FLT3 (IC50 = 44nM). Treatment of AML cells with SGI-1776 results in a concentration-dependent induction of apoptosis. Importantly, SGI-1776 is also cytotoxic in AML primary cells, irrespective of FLT3 mutation status and results in Mcl-1 protein decline. [1]Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction. Apoptosis induction coupled with the inhibition of RNA synthesis is observed in CLL cells treated with SGI-1776. [2] SGI-1776 exhibites cytotoxic activity in vitro with a median relative IC50 of 3.1 mM. SGI-1776 induces tumor growth inhibition meeting criteria for intermediate EFS T/C activity in 1 of 39 evaluable models. In contrast, SGI-1776 induces complete responses of subcutaneous MV4;11. [3] | |||||
| In vivo | Consistent with cell line data, xenograft model studies with mice bearing MV-4-11 tumors shows efficacy with SGI-1776. [1] SGI-1776 has shown preclinical activity against leukemia and solid tumor cell line models with IC50 values of 0.005–11.68 mM. SGI-1776 induces significant differences in EFS distribution in vivo in 9 of 31 solid tumor xenografts and in 1 of 8 of the evaluable ALL xenografts. [3] | |||||
| Features | ||||||
Protocol(Only for Reference)
Kinase Assay: [2]
| Kinase Assays | Kinase inhibition is measured by the use of radiometric assays performed by KinaseProfiler service. Assays contain a peptide substrate, known purified recombinant human kinases, gamma-labeled ATP, magnesium ion, and a fixed concentration (1 μM) of SGI-1776. In a final reaction volume of 25 μL, 5 to 10 mU of Pim1/2/3 is incubated with 8 mM of MOPS, pH 7.0; 0.2 mM ethylene diamine tetraacetic acid; 100 μM KKRNRTLTV;10 mM MgAcetate; and [γ-32P-ATP] . The reaction is initiated by the addition of the MgATP mix. After incubation for 40 minutes at room temperature, the reaction is stopped by the addition of 5 μL of a 3% phosphoric acid solution. Then, 10 μL of the reaction is spotted onto a P30 filtermat and washed 3 times for 5 minutes in 75 mM phosphoric acid and once in methanol before it is dried and measured via a scintillation counter. |
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Cell Assay: [1]
| Cell lines | MV-4-11, MOLM-13, and OCI-AML-3 cell lines |
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| Concentrations | 0.1-10 μM |
| Incubation Time | 24 hours |
| Method | Cells are cultured in IMDM (ATCC) supplemented with 10% FBS and grown in a 37oC incubator with 5% CO2. Cells are routinely tested for Mycoplasma infection using a commercially available kit. Cells are treated with DMSO or various concentrations of SGI-1776 for 24 hours. Cells (1×106) are washed, then resuspended in 100 μL of annexin binding buffer, mixed with 5 μL of FITC solution and 5 μL of propidium iodide (PI; 50 μg/mL) solution. For each sample, 1×104 cells are measured using a Becton Dickinson FACSCalibur flow cytometer. |
Animal Study: [1]
| Animal Models | Female cNOD-SCID mice |
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| Dosages | 75 mg/kg and 200 mg/kg |
| Administration | Administered via oral gavage (PO) on a daily ×5/week or twice/week schedu |
| Solubility | 30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL |
References
Chemical Information
Download SGI-1776 free base SDF
| Molecular Weight (MW) | 405.42 |
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| Formula | C20H22F3N5O |
| CAS No. | 1025065-69-3 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 81 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | 81 mg/mL (199 mM) | ||
| In vivo | 30% propylene glycol, 5% Tween 80, 65% D5W, | 30 mg/mL | |
| * <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. | |||
| Chemical Name | N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.40542 | 4.0542 | 8.1084 | 12.1626 |
Customer Reviews (1)
 Click to enlarge | Rating | |
| Source | Sci Signal 2011 Sep 4:rs9. SGI-1776 free base purchased from Selleck | |
| Method | ELISA | |
| Cell Lines | HeLa cells | |
| Concentrations | 1 μM | |
| Incubation Time | ||
| Results | Treatment of infected cells with kinase inhibitors directed at Akt (MK-2206), MEK(PD 98059), PKC(CEC), or Pim family kinases identified a dominant role for Pim family kinases in the release of IL-8 from Salmonella-infected epithelial cells. |
Product Citations (5)
Phosphoproteomic analysis of salmonella-infected cells identifies key kinase regulators and SopB-dependent host phosphorylation events. [Rogers LD, et al. Sci Signal 2011;4(191):rs9]
Phosphorylation of the androgen receptor by PIM1 in hormone refractory prostate cancer. [Ha S, et al. Oncogene 2012;32(34):3992-4000]
PIM kinase isoform specific regulation of MIG6 expression and EGFR signaling in prostate cancer cells. [Siu A, et al. Oncotarget
