Description
SGI-1776 free base can inhibit Pim1, Pim2, and Pim3 with IC50 of 7 nM, 363 nM and 9 nM.
Storage
2 years at -20centigrade Powder
Molecular Formula
C20H22F3N5O
Chemical Name
N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine
Solubility
DMSO 81 mg/mL Water
In vitro
SGI-1776 can potently inhibit Pim-1, Pim-2 and Pim-3 with IC50 of 7 nM, 363 nM and 69 nM. SGI-1776 also can inhibit Flt-3 and haspin with IC50 of 44 nM and 34 nM. SGI-1776, as an inhibitor of PIM kinase, shows inhibition to B-cell chronic lymphocytic leukemia (CLL). Pim kinases are over-expressed in B-cell chronic lymphocytic leukemia and inhibition of Pim kinases can affect the survival of B- cell. Besides inhibition to Pim kinases, the level of Mcl-1 protein can be markedly reduced by SGI-1776. Besides inhibition to kinases, SGI-1776 also shows inhibition to RNA synthesis. SGI-1776 can decrease in total RNA synthesis to approximately 50% of control at 10 umol/L.
In vivo
In AML cell lines (1) SGI-1776 can decrease phosphorylation of c-Myc and 4E-BP1. c-Myc(Ser62) phosphorylation was decreased by 50% relative to control at 0.1uM SGI-1776, which was further reduced by 80% with 1 uM. In MOLM-13 and OCI-AML-3 cell lines, and there was a signi?cant reduction in c-Myc phosphorylation after treatment with SGI-1776. Phosphorylation of translation regulator 4E-BP1 (Thr37/Thr46) was also decreased at 0.1uM SGI-1776 treatment in MV-4-11, MOLM-13 and OCI-AML-3. (2) SGI-1776 can induce apoptosis in AML cell lines. There was a dose-dependent increase in apoptotic cells after treatment with SGI-1776, and there was 25% increase in apoptosis with 10 uM SGI-1776. (3) The inhibition to FLT3-ITD by SGI-1776 is as potent as the inhibition to FLT3-ITD by AC220 in AML cell lines.
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