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General description
A cell-permeable indolylpyrimidinediamine compound that selectively suppresses cellular levels of GTP-bound Rac1 and Cdc42, but not RhoA, in serum-starved prostate cancer cultures upon EGF-stimulation (% of non-stimulated control Rac1-GTP level with/without 20 µM AZA1 = 56/375 in 22Rv1, 30/235 in DU 154, and 12/118 in PC-3 cells; % of non-EGF-stimulated control Cdc42-GTP level with/without 20 µM AZA1 = 15/170 in 22Rv1, 30/105 in DU 154, and 12/100 in PC-3 cells), resulting in effective suppression of PAK1, Akt, and BAD phosphorylations, as well as time- and dose-dependent (2 to 10 µM and up to 72 hr) growth inhibition of the cells in serum-deprived cultures with or without EGF stimulation. Dual Cdc42/Rac1 inhibition by AZA1 also effectively inhibits prostate cancer cells migration by decreasing cellular F-/G-actin ratio and disabling both filopodia and lamepodia formation. Daily intraperitoneal injection (100 µg/100 µL 30% DMSO/mouse) is shown to be efficacious in suppressing 22Rv1 tumor expansion in mice in vivo.
Biochem/physiol Actions
Cell permeable: yes
Reversible: yes
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
Other Notes
Zins, K., et al. 2013. PLoS One8, e74924.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
| assay | ≥95% (HPLC) |
| Quality Segment | 100 |
| form | powder |
| manufacturer/tradename | Calbiochem® |
| storage condition | OK to freeze,protect from light |
| color | light brown |
| solubility | DMSO: 100 mg/mL |
| storage temp. | 2-8°C |
| SMILES string | CC1=CC2=C(N1)C=CC(=C2)NC3=NC(=NC=C3)NC4=CC5=C(C=C4)NC(=C5)C |
| InChI | 1S/C22H20N6/c1-13-9-15-11-17(3-5-19(15)24-13)26-21-7-8-23-22(28-21)27-18-4-6-20-16(12-18)10-14(2)25-20/h3-12,24-25H,1-2H3,(H2,23,26,27,28) |
| InChI key | SYWHWWKOIJCMKF-UHFFFAOYSA-N |
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