受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C20H22F3N5O |
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分子量 | 405.42 | CAS No. | 1025065-69-3 | |
Solubility (25°C)* | 体外 | DMSO | 81 mg/mL (199.79 mM) | |
Ethanol | 81 mg/mL (199.79 mM) | |||
Water | Insoluble | |||
* <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. |
製品説明 | SGI-1776 free base is a novel ATP competitive inhibitor of Pim1 with IC50 of 7 nM in a cell-free assay, 50- and 10-fold selective versus Pim2 and Pim3, also potent to Flt3 and haspin. SGI-1776 induces apoptosis and autophagy. |
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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] |
キナーゼアッセイ | Kinase Assays | |
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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. | ||
細胞アッセイ | 細胞株 | MV-4-11, MOLM-13, and OCI-AML-3 cell lines |
濃度 | 0.1-10 μM | |
反応時間 | 24 hours | |
実験の流れ | 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. |
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動物実験 | 動物モデル | Female cNOD-SCID mice |
投薬量 | 75 mg/kg and 200 mg/kg | |
投与方法 | Administered via oral gavage (PO) on a daily ×5/week or twice/week schedu |
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Data from [Data independently produced by Oncogene, 2013, 32(34), 3992-4000]
Data from [Sci Signal, 2011, 4, rs9]
Data from [Data independently produced by Oncotarget, 2011, 2(12), 1134-44]
CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma [ Mol Cancer, 2023, 22(1):64] | PubMed: 36998071 |
Neoprzewaquinone A Inhibits Breast Cancer Cell Migration and Promotes Smooth Muscle Relaxation by Targeting PIM1 to Block ROCK2/STAT3 Pathway [ Int J Mol Sci, 2023, 24(6)5464] | PubMed: 36982538 |
Structure Activity Relationship Studies around DB18, a Potent and Selective Inhibitor of CLK Kinases [ Molecules, 2022, 27(19)6149] | PubMed: 36234686 |
Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy [ PLoS Negl Trop Dis, 2022, 16(10):e0010483] | PubMed: 36190997 |
Preclinical Immunopharmacologic Assessment of KPL-404, a Novel, Humanized, Non-Depleting Antagonistic Anti-CD40 Monoclonal Antibody [ Int J Gynecol Pathol, 2022, 10.1097/PGP.0000000000000882] | PubMed: 35443252 |
Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies [ Cancer Res, 2021, 81(23):6029-6043] | PubMed: 34625423 |
Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies [ Cancer Res, 2021, canres.1023.2021] | PubMed: 34625423 |
PIM1 phosphorylation of the androgen receptor and 14-3-3 ζ regulates gene transcription in prostate cancer [ Commun Biol, 2021, 4(1):1221] | PubMed: 34697370 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
The Global Phosphorylation Landscape of SARS-CoV-2 Infection [ Cell, 2020, 182(3):685-712.e19] | PubMed: 32645325 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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