| Stereochemistry | ACHIRAL |
| Molecular Formula | C20H22F3N5O |
| Molecular Weight | 405.4168 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CN1CCC(CNC2=NN3C(C=C2)=NC=C3C4=CC(OC(F)(F)F)=CC=C4)CC1
InChI
InChIKey=MHXGEROHKGDZGO-UHFFFAOYSA-N
InChI=1S/C20H22F3N5O/c1-27-9-7-14(8-10-27)12-24-18-5-6-19-25-13-17(28(19)26-18)15-3-2-4-16(11-15)29-20(21,22)23/h2-6,11,13-14H,7-10,12H2,1H3,(H,24,26)
| Molecular Formula | C20H22F3N5O |
| Molecular Weight | 405.4168 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
SGI-1776 is a PIM-kinase inhibitor, developed by SuperGen Inc. SGI-1176 was tested in clinical trials against relapsed/refractory leukemias, prostate cancer and Non Hodgkin's Lymphoma, but the dose limiting toxicity of cardiac QTc prolongation was identified and clinical development of SGI-1776 was terminated.
Originator
Approval Year
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
Tox targets
PubMed
Patents
Sample Use Guides
In clinical trial SGI-1776 was administered orally at escalating dose levels ranging from 350 to 1600 mg/day. Clinical trial was prematurely terminated due to unacceptable toxicity of SGI-1776.
Route of Administration:
Oral
CLL cells were treated with DMSO alone or with 0.3, 1, 3, or 10 μmol/L SGI-1776 for 24 hours. Cells (10^6) were washed, resuspended in 100 μL of annexin binding buffer, and mixed with 5 μL of annexin–fluorescein isothiocyanate (FITC) solution and 5 μL of propidium iodide solution with 2.5 μg/mL DNase-free RNase A (Roche). At least 10 000 cells were measured per sample by the use of a Becton Dickinson FACSCalibur flow cytometer. Caspase inhibitor N-benzyloxycarbonyl-valyl-alanyl-aspartyl-fluoromethylketone (ZVAD) was obtained from Alexis Biochemicals, and cells were treated with DMSO alone or 25 μmol/L ZVAD with or without 10 μmol/L SGI-1776 treatment for 24, 48, and 72 hours and then analyzed by flow cytometry. In vitro incubation of primary CLL cells (n = 7), with 1, 3, and 10 μmol/L SGI-1776 for 24 hours resulted in an average increase in apoptosis of 10%, 22%, and 38%, respectively, compared with untreated cells.
