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AI-10-49

Cat.No.S7814

AI-10-49 is a selective inhibitor of the binding of CBFβ-SMMHC to RUNX1 with IC50 of 260 nM.
AI-10-49 Chemical Structure

Chemical Structure

Molecular Weight: 660.52

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Chemical Information, Storage & Stability

Molecular Weight 660.52 Formula

C30H22F6N6O5

 Storage (From the date of receipt)
CAS No. 1256094-72-0 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles FC(F)(F)OC1=CC=C2[NH]C(=NC2=C1)C3=NC=C(OCCOCCOC4=CN=C(C=C4)C5=NC6=C([NH]5)C=CC(=C6)OC(F)(F)F)C=C3

Solubility

In vitro
Batch:

DMSO : 62 mg/mL (93.86 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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Mechanism of Action

Targets/IC50/Ki
CBFβ-SMMHC [1]
260 nM
CBFβ-SMMHC/RUNX1 [1]
(in FRET assay)
0.26 μM
In vitro
AI-10-49 displays specific growth inhibition of inv(16)-positive cell line ME-1. This compound selectively binds to CBFβ-SMMHC, disrupts its binding to RUNX1, and restores RUNX1 transcriptional activity. [1]
Kinase Assay
FRET assays
Cerulean-Runt domain is expressed and purified. Venus-CBFβ-SMMHC is constructed by inserting 6xHis tag and Venus into pET22b vector between NdeI and NcoI sites, and by inserting CBFβ-SMMHC (the CBFβ-SMMHC construct contains 369 amino acids, 1-166 from CBFβ and 166-369 from MYH11 (amino acids 1526-1730)) between the NcoI and BamHI sites. The fusion protein is purified by standard Ni-affinity chromatography with an on column benzonase treatment to remove residual DNA contaminants. Proteins are dialyzed into FRET buffer (25mM Tris-HCl, pH 7.5, 150mM KCl, 2mM MgCl2) prior to use. Protein concentrations are determined by UV absorbance of the Cerulean and Venus at 433 and 513 nm, respectively. Cerulean-Runt domain and Venus-CBFβ-SMMHC were mixed 1:1 to achieve a final concentration of 10 nM in 96 well black COSTAR plates. DMSO solutions of this compound are added to a final DMSO concentration of 5% (v/v) and the plates incubated at room temperature for one hour in the dark. A PHERAstar microplate reader is used to measure fluorescence (excitation at 433 nm and emission measured at 474 and 525 nm). For IC50 determinations, the ratios of the fluorescence intensities at 525 nm and 474 nm are plotted versus the log of this chemical concentration, and the resulting curve was fit to a sigmoidal curve using Origin7.0. Three independent measurements are performed and their average and deviation are used for IC50 data fitting.
In vivo
In mice transplanted with Cbfb+/MYH11;Nras+/G12D leukemic cells, AI-10-49 (200 mg/kg, i.p.) reduces leukemia expansion. [1]
References

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