BMS-509744 |
| Catalog No.GC10455 |
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 439575-02-7
Sample solution is provided at 25 µL, 10mM.
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BMS-509744 is a selective inhibitor of ITK with IC50 value of 15 nM [1].
ITK (IL-2-inducible T cell kinase) is an enzyme and plays an important role in T cell receptor signaling. It has been reported that ITK involves in the Th2-mediated inflammatory process and thus be regarded as a promising target for Th2-mediated inflammatory/immunosuppressive diseases treatment, such as asthma, rhinitis, allergies and atopic dermatitis [2].
BMS-509744 is a potent ITK inhibitor and is different from the reported ITK inhibitor RO5191614. When tested with human and murine cells, administration of BMS-509744 reduced TCR-induced functions by functioning on PLCgamma1 tyrosine phosphorylation, calcium mobilization, IL-2 secretion and T-cell proliferation [2]. In wild-typr HIV1 infected cells, BMS-509744 treatment blocked its infectivity and replication by inhibiting ITK, while has no effect on Nef-defective HIV1 infected cells [3].
In mouse model of ovalbuim-induced allergy/asthma, administration of BMS-509744 suppressed the production of IL-2 and significantly diminished lung inflammation by inhibiting ITK activity [2].
References:
[1].Kutach, A.K., et al., Crystal structures of IL-2-inducible T cell kinase complexed with inhibitors: insights into rational drug design and activity regulation. Chem Biol Drug Des, 2010. 76(2): p. 154-63.
[2].Lin, T.A., et al., Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry, 2004. 43(34): p. 11056-62.
[3].Tarafdar, S., J.A. Poe, and T.E. Smithgall, The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner. J Biol Chem, 2014. 289(22): p. 15718-28.
| Cell experiment [1]: | |
|
Cell lines |
Jurkat T cells and A549 lung carcinoma cells |
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Preparation method |
This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.1 ~ 10 μM |
|
Applications |
In Jurkat T-cells, BMS-509744 dose-dependently inhibited tyrosine phosphorylation of phospholipase Cγ1 (PLCγ1) induced by anti-CD3 antibodies. In A549 lung carcinoma cells, Itk expression of which was not evident, BMS-509744 did not exhibit significant inhibition on cellular tyrosine or PLCγ1 phosphorylation induced by epidermal growth factors, at the concentration even up to 10 μM. |
| Animal experiment [1]: | |
|
Animal models |
Mice |
|
Dosage form |
5, 25 and 50 mg/kg; s.c. or i.p.; b.i.d., for 3 days |
|
Applications |
In mice treated with anti-CD3 antibodies, BMS-509744 at the dose of 50 mg/kg inhibited IL-2 production by 50%. In a mouse model of ovalbumin-induced allergy/asthma, BMS-509744 dose-dependently reduced total cell and eosinophil infiltration into the lung, which indicated reduced lung inflammation. The reduction reached statistical significance at the dose of 25 mg/kg administered subcutaneously. |
|
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]. Lin, T.A., et al., Selective Itk inhibitors block T-cell activation and murine lung inflammation. Biochemistry, 2004. 43(34): p. 11056-62. | |
| Cas No. | 439575-02-7 | SDF | |
| Chemical Name | N-(5-((5-(4-acetylpiperazine-1-carbonyl)-4-methoxy-2-methylphenyl)thio)thiazol-2-yl)-4-(((3,3-dimethylbutan-2-yl)amino)methyl)benzamide | ||
| Canonical SMILES | CC1=C(SC(S2)=CN=C2NC(C3=CC=C(CNC(C(C)(C)C)C)C=C3)=O)C=C(C(N4CCN(C(C)=O)CC4)=O)C(OC)=C1 | ||
| Formula | C32H41N5O4S2 | M.Wt | 623.83 |
| Solubility | DMSO : 21.9 mg/mL (35.11 mM; Need ultrasonic and warming) | 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. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.603 mL | 8.015 mL | 16.03 mL |
| 5 mM | 0.3206 mL | 1.603 mL | 3.206 mL |
| 10 mM | 0.1603 mL | 0.8015 mL | 1.603 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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.)
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.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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