Home>>Signaling Pathways>> Others>>AI-10-49

AI-10-49

Catalog No.GC11189

Inhibitor of CBFβ –SMMHC and RUNX1 interaction

Products are for research use only. Not for human use. We do not sell to patients.

AI-10-49 Chemical Structure

Cas No.: 1256094-72-0

Size Price Stock Qty
10mM (in 1mL DMSO)
$155.00
In stock
5mg
$55.00
In stock
10mg
$103.00
In stock
25mg
$196.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

Cell lines

ME-1 (human leukemia cell lines)

Preparation method

Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

6 h

Applications

After 6 hours of treatment, AI-10-49 effectively dissociates RUNX1 from CBFb-SMMHC with 90% dissociation, by contrast, it has a mild effect on CBFb-RUNX1 association. The ChIP assays indicates that AI-10-49 treatment on ME-1 cells for 6 hours increases RUNX1 occupancy 8-, 2.2-, and 8-fold at the RUNX3, CSF1R, and CEBPA promoters.

Animal experiment [1]:

Animal models

Transplanted mice with Cbfb+/MYH11:Ras+/G12D leukemic cells

Dosage form

200 mg/kg; 10 days

Applications

Mice treated with AI-10-49 survives markedly longer (median latency = 61 days) and transient AI-10-49 treatment also reduces leukemia spreading in vivo.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

1. Illendula A, Pulikkan JA, Zong H et.al A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-84.

Background

AI-10-49 is a selective inhibitor of CBFβ –SMMHC and RUNX1 interaction with a FRET IC50 value of 260nM.
AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient with AI-10-49 triggers selective cell death. Direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. The stability of RUNX1, CBFb, and CBFb-SMMHC was not affected by AI-10-49 [1].
In 11 human leukemia cell lines, ME-1 cells were the only cell line highly sensitive to AI-10-49. In ME-1 cell, AI-10-49 has enhanced inhibitory activity on growth (IC50 = 0.6 mM) compared with the parent protonated bivalent compound AI-4-83 (IC50 of ~3 mM). In normal human bone marrow cells, AI-10-49 showed negligible activity (IC50 > 25 mM), which indicated a robust potential therapeutic window. In chromatin-immunoprecipitation (ChIP) assays, treatment of ME-1 cells for 6 hours with AI-10-49 increased RUNX1 occupancy 8-, 2.2-, and 8-fold at the RUNX3, CSF1R, and CEBPA promoters, respectively.
After treatment with AI-10-49 to leukemia mice significantly prolonged their lives, and after 7 days of administration of AI-10-49, we observe no evidence of toxicity [1].
Reference:
1.Illendula A, Pulikkan JA, Zong H et al. A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice. Science. 2015 Feb 13;347(6223):779-784.

Chemical Properties

Cas No. 1256094-72-0 SDF
Chemical Name 2,2'-(5,5'-((oxybis(ethane-2,1-diyl))bis(oxy))bis(pyridine-5,2-diyl))bis(5-(trifluoromethoxy)-1H-benzo[d]imidazole)
Canonical SMILES FC(F)(F)OC1=CC2=C(C=C1)NC(C(C=C3)=NC=C3OCCOCCOC(C=C4)=CN=C4C5=NC6=CC(OC(F)(F)F)=CC=C6N5)=N2
Formula C30H22F6N6O5 M.Wt 660.52
Solubility ≥ 16.53mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.514 mL 7.5698 mL 15.1396 mL
5 mM 0.3028 mL 1.514 mL 3.0279 mL
10 mM 0.1514 mL 0.757 mL 1.514 mL
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for AI-10-49

Average Rating: 5 ★★★★★ (Based on Reviews and 32 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for AI-10-49

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.