AZD-5438 (Synonyms: AZD 5438;AZD5438) |
| Catalog No.GC12438 |
AZD-5438 es un potente inhibidor de CDK1, CDK2 y CDK9, con IC50 de 16 nM, 6 nM y 20 nM en ensayos sin células, respectivamente. AZD-5438 muestra menos actividad de inhibiciÓn frente a GSK3β, CDK5 y CDK6.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 602306-29-6
Sample solution is provided at 25 µL, 10mM.
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AZD5438 is a potent small molecule inhibitor of cyclin-dependent kinase (CDK) 1, 2 and 9 with half maximal inhibitory concentration IC50 of 16 nmol/L, 6 nmol/L and 20 nmol/L respectively. AZD5438 has also been found to potently inhibit the human cyclin E/CDK2 complex, the cyclin B1/CDK1 complex and the cyclin A/CDK2 complex with IC50 of 0.006 μM, 0.016 μM and 0.045 μM respectively. In previous studies, AZD5438 has exhibited significant anti-proliferative activity in a few human tumor cell lines with IC50 ranging from 0.2 μmol/L to 1.7 μmol/L, in which the phosphorylation of a few proteins, including CDK substrates pRb, nucleolin, protein phosphatase 1a and RNA polymerase II COOH-terminal domain, and cell cycling at G2-M, S and G1 phases were inhibited.
References:
[1]Camidge DR1, Smethurst D, Growcott J, Barrass NC, Foster JR, Febbraro S, Swaisland H, Hughes A. A first-in-man phase I tolerability and pharmacokinetic study of the cyclin-dependent kinase-inhibitor AZD5438 in healthy male volunteers. Cancer Chemother Pharmacol. 2007 Aug;60(3):391-8. Epub 2006 Nov 18.
[2]Byth KF, Thomas A, Hughes G, Forder C, McGregor A, Geh C, Oakes S, Green C, Walker M, Newcombe N, Green S, Growcott J, Barker A, Wilkinson RW. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts. Mol Cancer Ther. 2009 Jul;8(7):1856-66. doi: 10.1158/1535-7163.MCT-08-0836. Epub 2009 Jun 9.
| Cell experiment [1]: | |
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Cell lines |
MCF-7 breast cancer cells, |
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Preparation method |
The solubility of this compound in DMSO is >18.6mg/mL. 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. |
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Reacting condition |
48 h |
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Applications |
AZD5438 induced cell cycle arrest by inhibiting phosphorylation of cdk-dependent substrates, and exhibited the broad antiproliferative activity against asynchronous LoVo, MCF-7 and SW620 tumor cell lines. AZD5438 showed antiproliferative in a range of tumor cell lines including lung, colorectal, breast, prostate, and hematologic tumors with IC50 ranging from 0.2 μM (MCF-7) to 1.7 μM (ARH-77). |
| Animal experiment [1]: | |
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Animal models |
Female nude mice bearing established BT474c, Colo-205, HX147, PC-3, and SW620 human tumor xenografts |
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Dosage form |
Oral gavage, 37.5–75 mg/kg, once or twice daily for 3 wk |
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Application |
In vivo, oral treatment of AZD5438 significantly inhibited the growth of human tumor xenografts derived from a wide range of different cancer types including breast, colon, lung, prostate, and ovarian with maximum TGI ranging from 38% to 153%. In the SW620 xenograft model, AZD5438 inhibited several cell cycle proteins such as, phH3, phosphonucleolin, PP1a, and several phospho-pRb epitopes in a dose-dependent manner. |
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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. |
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References: [1]. Byth K F, Thomas A, Hughes G, et al. AZD5438, a potent oral inhibitor of cyclin-dependent kinases 1, 2, and 9, leads to pharmacodynamic changes and potent antitumor effects in human tumor xenografts[J]. Molecular cancer therapeutics, 2009, 8(7): 1856-1866. | |
| Cas No. | 602306-29-6 | SDF | |
| Sinónimos | AZD 5438;AZD5438 | ||
| Chemical Name | 4-(2-methyl-3-propan-2-ylimidazol-4-yl)-N-(4-methylsulfonylphenyl)pyrimidin-2-amine | ||
| Canonical SMILES | CC1=NC=C(N1C(C)C)C2=NC(=NC=C2)NC3=CC=C(C=C3)S(=O)(=O)C | ||
| Formula | C18H21N5O2S | M.Wt | 371.46 |
| Solubility | ≥ 18.55mg/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. |
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| 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 | 2.6921 mL | 13.4604 mL | 26.9208 mL |
| 5 mM | 0.5384 mL | 2.6921 mL | 5.3842 mL |
| 10 mM | 0.2692 mL | 1.346 mL | 2.6921 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)
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