General description
A cell-permeable compound that selectively induces apoptosis in AML (Acute Myelogenous Leukemia) with little effect on normal CD34+ AML progenitor cells. Shown to directly inhibit both PDK1 and Akt activities in in vitro kinase assays in a dose-dependent manner and block cellular phosphorylation of Akt at both Ser473 and Thr308. The dual inhibition nature against both PDK1/Akt and Flt3/PIM signaling pathways allows effective killing of AML cells (Average IC50 = 1.05, 1.91, and 0.43 µM for AML with wild-type Flt3, single mutant ITD/D835, and double mutant Flt3-ITD-TDK, respectively) that are otherwise resistant to inhibitors that target only the PDK1/Akt pathway. CAS. No. 331253-86-2 and 329710-24-9.
CAS. Nos. 331253-86-2 and 329710-24-9 (two isomers)
Biochem/physiol Actions
Cell permeable: yes
Primary Target
Both PDK1 and Akt activities
Product does not compete with ATP.
Reversible: no
Target IC50: 1.05, 1.91, and 0.43 µM for AML with wild-type Flt3, single mutant ITD/D835, and double mutant Flt3-ITD-TDK, respectively
Packaging
Packaged under inert gas
Other Notes
Zeng, Z., et al. 2006. Cancer Res.66, 3737.
Koul, D., et al. 2006. Mol. Cancer Ther.5, 637.
Mandal. M., et al. 2006. Oral Oncol.42, 430.
Mandal. M., et al. 2005. Br. J. Cancer92, 1899.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Irritant (B)
| Quality Segment | 100 |
| assay | ≥98% (sum of two isomers, HPLC) |
| form | solid |
| manufacturer/tradename | Calbiochem® |
| storage condition | OK to freeze,protect from light |
| color | yellow |
| solubility | DMSO: 10 mg/mL |
| shipped in | ambient |
| storage temp. | 2-8°C |
| SMILES string | [n]21nnnc2nc3c(n1)c4c(cccc4)C3=O |
| InChI | 1S/C10H4N6O/c17-9-6-4-2-1-3-5(6)7-8(9)11-10-12-14-15-16(10)13-7/h1-4H |
| InChI key | SSNMLKNJEUSPDY-UHFFFAOYSA-N |
