AURORA A/MYCN DUAL INHIBITOR CD532 (C15-1305-080)

General description

A cell permeable diaminopyrimidine derived compound that acts as a highly potent and selective inhibitor of Aurora A (IC₅₀ = 48 nM). Acts by binding to the hinge region via a pyrazole moiety and stabilizes a DFG-in, inactive conformation of Aurora A. Potentiates the loss of the wild-type MYCN protein by disrupting MYCN-Aurora A complex and allowing its ubiquitination and proteasomal degradation in MYCN-amplified SK-N-BE (2) and Kelly neuroblastoma cells (EC₅₀ = 223 and 146.7 nM, respectively). Causes a loss of S-phase entry of cells and allows their accumulation in both G0/G1 and G2 phases. Shown to be effective in vivo with serum t1/2 = 1.5 h in mice.

A cell permeable diaminopyrimidine derived compound that acts as a highly potent and selective inhibitor of Aurora A (IC₅₀ = 48 nM). Acts by binding to the hinge region via a pyrazole moiety and stabilizes a DFG-in, inactive conformation of Aurora A. Potentiates the loss of the wild-type MYCN protein by disrupting MYCN-Aurora A complex and allowing its ubiquitination and proteasomal degradation in MYCN-amplified SK-N-BE (2) and Kelly neuroblastoma cells (EC₅₀ = 223 and 146.7 nM, respectively). Causes a loss of S-phase entry of cells and allows their accumulation in both G0/G1 and G2 phases. Shown to be effective in vivo with serum t_1/2 = 1.5 h in mice.

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Biochem/physiol Actions

Cell permeable: yes

Primary Target
Aurora A

Reversible: yes

Secondary Target
MYCN

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Lee, J.K., et al. 2016. Cancer Cell.29, In press.
Gustafson, W. C., et al. 2014. Cancer Cell.26, 414.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Molecular Weight: 522.52. Empirical Formula: C₂₆H₂₅F₃N₈O. Assay: ≥. 97% (HPLC). Quality Level: 100. form: solid. potency: 48 . nM IC₅₀. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: tan. solubility: DMSO: 50 . mg/mL. storage temp.: 2-8°C. SMILES string: O: C(NC1: CC: CC(C(F)(F)F): C1)NC2: CC: C(NC3: NC: CC(NC4: NNC(C5CCCC5): C4): N3)C: C2. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.