SGI-1776 free base

Catalog No.S2198

For research use only.

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. Phase 1.

SGI-1776 free base Chemical Structure

CAS No. 1025065-69-3

Selleck's SGI-1776 free base has been cited by 36 publications

Purity & Quality Control

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Biological Activity

Description 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. Phase 1.
Targets
Pim1 [1]
(Cell-free assay)
FLT3 [1]
(Cell-free assay)
Pim3 [1]
(Cell-free assay)
Pim2 [1]
(Cell-free assay)
7 nM 44 nM 69 nM 363 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO cells M33mXGZ2dmO2aX;uJIF{e2G7 M4\oemlvcGmkaYTpc44hd2ZiaIXtZY4hTVKJIHX4dJJme3OnZDDpckBEUE9iY3XscJMh[nliYYX0c41ifGWmIIDheINpKGOuYX3wJI1mfGixZDygTWM2OD1zIN88US=> NUT2dnNUOjV3OEm5N|I>
Assay
Methods Test Index PMID
Western blot c-Myc (Ser62) / c-Myc / p-Histone H3 (Ser10) / Histone H3 / Bad(Ser112) / Bad / 4E-BP1 ; Mcl-1 ; Cell viability ; p70-S6K / p-P70S6K / rpS6 / p-rpS6 22955922 22015557 27120806
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]

Protocol (from 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.

Cell Research:[1]
  • Cell lines: MV-4-11, MOLM-13, and OCI-AML-3 cell lines
  • 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 Research:[1]
  • Animal Models: Female cNOD-SCID mice
  • Dosages: 75 mg/kg and 200 mg/kg
  • Administration: Administered via oral gavage (PO) on a daily ×5/week or twice/week schedu

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
30% propylene glycol, 5% Tween 80, 65% D5W
For best results, use promptly after mixing.

30 mg/mL

Chemical Information

Molecular Weight 405.42
Formula

C20H22F3N5O

CAS No. 1025065-69-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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