AZ 628 (Synonyms: AZ-628; AZ628) |
| Catalog No.GC15055 |
Raf kinases,potent and ATP-competitive
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 878739-06-1
Sample solution is provided at 25 µL, 10mM.
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AZ628 is a potent and newly discorvered inhibitor of BRAF, c-Raf-1 and BRAFV600E with IC50 values of 105 nM, 29 nM and 34 nM, respectively. This compound prevents CRAF activation through persistently occupying the ATP-binding site of Raf kinase. Specificity profile suggests that AZ628 also inhibits activation of other tyrosine protein kinases such as DDR2, VEGFR2, Lyn, Flt1, FMS and others.
Raf kinases a family of three serine/threonine-specific protein kinases and participate in the RAS-RAF-MEK-ERK signal transduction cascade, also known as the mitogen-activated protein kinase (MAPK) cascade. The activation of MAPK signaling leads to different cellular response such as cell proliferation, apoptosis and inflammation.
AZ628 has the potent anti-tumor activity. In human colon and melanoma-derived cell line that carries the recurrent V600E activating BRAF mutation, AZ628 was shown to inhibit anchorage-dependent and -independent growth, induce cell cycle arrest, and cause apoptosis [1]. AZ628 may be antiangiogenic due to inhibition of VEGFR2 [2].
Generation of melanoma cell line clones is obtained resistance to the RAF kinase inhibitor AZ628. Resistance to AZ628 is connected with raised levels of the RAF downstream effector p-ERK1/2. ERK1/2 initiation in AZ628-resistant clones is interceded by MEK. Supported multiplication of AZ628-resistant clones is to a great extent autonomous of BRAF kinase action. AZ628-resistant clones express elevated CRAF. Survival of AZ628-safe cells is subject to CRAF [1].
References:
1. Montagut C, Sharma SV, Shioda T, McDermott U, Ulman M, Ulkus LE, et al. Elevated CRAF as a potential mechanism of acquired resistance to BRAF inhibition in melanoma. Cancer Res 2008,68:4853-4861.
2. Khazak V, Astsaturov I, Serebriiskii IG, Golemis EA. Selective Raf inhibition in cancer therapy. Expert Opin Ther Targets 2007,11:1587-1609.
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Cell experiment: |
Cell viability quantified by Syto60 after 72 hours of AZ 628 (0.5, 1.0, and 1.5 μM), CI-1040 or BAY61-3606 treatment in HCT-116 (K-RASG13D/+) or HKe-3 (K-RAS-/+) cell lines. Relative cell viability is normalized to DMSO vehicle treated control for each cell line[2]. |
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References: [1]. Khazak V, et al. Selective Raf inhibition in cancer therapy. Expert Opin Ther Targets. 2007 Dec;11(12):1587-609. |
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| Cas No. | 878739-06-1 | SDF | |
| Synonyms | AZ-628; AZ628 | ||
| Chemical Name | 3-(2-cyanopropan-2-yl)-N-[4-methyl-3-[(3-methyl-4-oxoquinazolin-6-yl)amino]phenyl]benzamide | ||
| Canonical SMILES | CC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)C(C)(C)C#N)NC3=CC4=C(C=C3)N=CN(C4=O)C | ||
| Formula | C27H25N5O2 | M.Wt | 451.53 |
| Solubility | ≥ 22.6mg/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 | 2.2147 mL | 11.0735 mL | 22.1469 mL |
| 5 mM | 0.4429 mL | 2.2147 mL | 4.4294 mL |
| 10 mM | 0.2215 mL | 1.1073 mL | 2.2147 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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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 36 reference(s) in Google Scholar.)
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