product name AZD1208
Description: AZD1208 is a potent, and orally available small molecule inhibitor of Pim kinase with IC50 of 0.4 nM, 5 nM, and 1.9 nM for Pim1, Pim2, and Pim3 in cell-free assays, respectively. AZD1208 has potential antineoplastic activity. Pan-PIM kinase inhibitor AZD1208 inhibits the activities of PIM1, PIM2 and PIM3 serine/threonine kinases, which may result in the interruption of the G1/S phase cell cycle transition, thereby causing cell cycle arrest and inducing apoptosis in cells that overexpress PIMs.
References: Blood. 2014 Feb 6;123(6):905-13.
379.48
Formula
C21H21N3O2S
CAS No.
1204144-28-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 75 mg/mL (197.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :
| In Vitro |
In vitro activity: AZD1208 is an orally available, potent and highly selective Pim inhibitor that effectively inhibits all three isoforms. AZD1208 inhibits the growth of several AML cell lines and sensitivity correlates with the level of Pim-1 expression, STAT5 activation and presence of protein tyrosine kinase mutation. AZD1208 causes cell cycle arrest and apoptosis in MOLM-16 cells in culture. This is accompanied by a dose-dependent reduction in phosphorylation of BAD, 4EBP1 and p70S6K. In addition, AZD1208 leads to potent inhibition of colony growth of primary AML cells from bone marrow aspirates and downregulates phosphorylation of Pim targets. Kinase Assay: The activity of purified human Pim-1, -2, and -3 enzymes on a BAD peptide substrate was determined as previously described. To determine inhibition constants (Ki), 50% inhibition concentration (IC50) values were acquired at a series of adenosine triphosphate (ATP) concentrations and compound doses with 1 nM enzyme and 1.5 µM full-length BAD substrate in 50 mM N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid, 1 mM dithiothreitol, 0.01% Tween 20, 50 μg/mL bovine serum albumin, and 10 mM MgCl2. The Ki values were calculated by global data fitting using the Cheng-Prusoff equation or the Morrison equation for tight-binding inhibitors. To assess selectivity, 442 kinases were screened by using DiscoveRx KINOMEscan technology at a single concentration of 1 μM. Kinases inhibited by more than 50% were retested at DiscoveRx with a full dose-response to determine binding affinity. Cell Assay: |
|---|---|
| In Vivo | AZD1208 suppresses the growth of MOLM-16 and KG-1a xenograft tumors in vivo in a dose proportional manner. |
| Animal model | Female CB17 SCID mice implanted with MOLM-16 cells (5 × 106) or KG-1a cells (6 × 106) |
| Formulation & Dosage | Dissolved in 0.5% hydroxypropyl methylcellulose; 30 mg/kg twice per week; oral gavage |
| References | Blood. 2014 Feb 6;123(6):905-13. |
