U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

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
Structure of SGI-1776

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)

HIDE SMILES / InChI

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

Description

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

Targets

Primary TargetPharmacologyConditionPotency
7.0 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown
Primary
Unknown
Primary
Unknown

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.
Substance Class Chemical
Record UNII
72AUA0603W
Record Status Validated (UNII)
Record Version