product name SMI-4a
Description: SMI-4a is a potent and selective inhibitor of Pim1 with IC50 of 17 nM, it is modestly potent to Pim-2, and does not significantly inhibit any other serine/threonine- or tyrosine-kinases. SMI-4a blocks the growth of precursor T-cell lymphoblastic leukemia/lymphoma. SMI-4a was found to induce phosphorylation of extracellular signal-related kinase1/2 (ERK1/2).
References: Mol Cancer Ther. 2009 Jun;8(6):1473-83; Blood. 2010 Jan 28;115(4):824-33.
273.23
Formula
C11H6F3NO2S
CAS No.
438190-29-5
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 55 mg/mL (201.3 mM)
Water: <1 mg/mL
Ethanol: 32 mg/mL (117.1 mM)
Solubility (In vivo)
30% propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
TCS PIM-1 4a
other peoduct :
| In Vitro |
In vitro activity: SMI-4a is an ATP competitive inhibitor of Pim1 with IC50 of 17 nM. SMI-4a shows high selectivity for Pim1 against a panel of kinases. SMI-4a inhibits the in vitro phosphorylation by Pim-1 of the known substrate, the translational repressor 4E-BP1. SMI-4a (5μM) inhibits pancreatic and leukemic cells growth. SMI-4a reduces phosphorylation of the Pim target Bad in prostate and hematopoietic cells. SMI-4a causes cell cycle arrest and reverses the antiapoptotic activity of Pim-1. SMI-4a increases the amount of p27Kip1 in the nucleus. SMI-4a treatment of pre-T-LBL inhibits the mTOR pathway. SMI-4a reduces MYC protein expression in pre-T-LBL. SMI-4a treatment induces up-regulation of MAPK pathway Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | SMI-4a (60 mg/Kg) treatment twice daily significantly reduce tumor size and is well tolerated. Tumors harvested 1 hour after the final oral gavage of SMI-4a demonstrates decreased phosphorylation of p70 S6K compared with tumors from mice treated with vehicle, whereas in comparison total p70 S6K expression isunchanged. |
| Animal model | Nu/nu nude mice injected with pre-T-LBL cells |
| Formulation & Dosage | Dissolved in 65% DMSO, 30% PEG-400, 5% Tween-80; 75, 60 mg/kg; oral administration |
| References | Mol Cancer Ther. 2009 Jun;8(6):1473-83; Blood. 2010 Jan 28;115(4):824-33. |
