Home JAK/STAT Pim inhibitor - Autophagy activator - Apoptosis related activator - Haspin Kinase inhibitor - FLT3 inhibitor SGI-1776 free base For research use only.

SGI-1776 free base

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.

SGI-1776 free base Chemical Structure

SGI-1776 free base Chemical Structure

CAS No. 1025065-69-3

Purity & Quality Control

SGI-1776 free base Related Products

Signaling Pathway

Pim Signaling Pathways

Pim Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
CHO cells Function assay Inhibition of human ERG expressed in CHO cells by automated patch clamp method, IC50=1 μM 25589932
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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.
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 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]
Kinase Assay 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 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p70-S6K / p-P70S6K / rpS6 / p-rpS6 Cell viability Mcl-1 c-Myc (Ser62) / c-Myc / p-Histone H3 (Ser10) / Histone H3 / Bad(Ser112) / Bad / 4E-BP1 27120806
In Vivo
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]
Animal Research 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

Chemical Information & Solubility

Molecular Weight 405.42 Formula

C20H22F3N5O
CAS No. 1025065-69-3 SDF Download SGI-1776 free base SDF
Smiles CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 81 mg/mL ( (199.79 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 81 mg/mL

Water : Insoluble


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