Senexin ACDK8 inhibitor CAS# 1366002-50-7 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1366002-50-7 | SDF | Download SDF |
| PubChem ID | 56927063 | Appearance | Powder |
| Formula | C17H14N4 | M.Wt | 274.3 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 100 mg/mL (364.54 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | 4-(2-phenylethylamino)quinazoline-6-carbonitrile | ||
| SMILES | C1=CC=C(C=C1)CCNC2=NC=NC3=C2C=C(C=C3)C#N | ||
| Standard InChIKey | XBJCNHGQFJFCOY-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C17H14N4/c18-11-14-6-7-16-15(10-14)17(21-12-20-16)19-9-8-13-4-2-1-3-5-13/h1-7,10,12H,8-9H2,(H,19,20,21) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Senexin A is a CDK8 inhibitor with an IC50 of 280 nM.In Vitro:Senexin A inhibits CDK8 and CDK19 ATP site binding with Kd50 of 0.83 μM and 0.31 μM, respectively and CDK8 kinase activity with IC50 of 0.28 μM. Senexin A inhibits β-catenin–dependent transcription in HCT116 colon carcinoma cells. The induction of transcription factor EGR1 upon serum starvation, followed by readdition of serum, is strongly inhibited by Senexin A in HT1080 cells. Senexin A inhibits only p21-induced transcription but not other biological effects of p21. Senexin A also decreases the expression of many secreted tumor-promoting factors in doxorubicin-treated wild-type HCT116 cells[1].In Vivo:Five daily treatment of Senexin A fully reverses tumor-promoting effect of chemotherapy. Senexin A shows no detectable toxicity and no significant effects on body weight, organ weights, or blood cell counts in C57BL/6 mice during the treatment. This effect of doxorubicin treatment is completely abolished, however, when doxorubicin injection is followed by administration of Senexin A. Senexin A treatment strongly improves the response of A549/MEF tumors to doxorubicin[1]. References: | |||||
Senexin A Dilution Calculator
Senexin A Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 3.6456 mL | 18.2282 mL | 36.4564 mL | 72.9129 mL | 91.1411 mL |
| 5 mM | 0.7291 mL | 3.6456 mL | 7.2913 mL | 14.5826 mL | 18.2282 mL |
| 10 mM | 0.3646 mL | 1.8228 mL | 3.6456 mL | 7.2913 mL | 9.1141 mL |
| 50 mM | 0.0729 mL | 0.3646 mL | 0.7291 mL | 1.4583 mL | 1.8228 mL |
| 100 mM | 0.0365 mL | 0.1823 mL | 0.3646 mL | 0.7291 mL | 0.9114 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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IC50: 280 nM
Senexin A is a Cyclin-dependent kinase 8 (CDK8) inhibitor.
CDK8 is an oncogenic CDK family member that plays no role in cell-cycle progression but regulates several transcriptional programs involved in carcinogenesis and the stem-cell phenotype. CDK8 also cooperates in the formation of internucleolar bodies, where CDK8 accumulates.
In vitro: Senexin A inhibited p21-caused induction of CMV-GFP when GFP expression was normalized either by relative cell number or by the protein amount. p21 was shown to activate NF-κB–dependent transcription, and Senexin A could inhibit p21-stimulated activity of the consensus NF-κB–dependent promoter. Senexin A had no effect on p21 induction by IPTG, on p21-induced senescent phenotype, or on cell growth with or without p21 [1].
In vivo: Previous study tested Senexin A combined with MEF for the in vivo chemosensitization of xenografts formed by tumor cells. SCID mice were injected with A549 cells mixed with MEF. Once tumors stably formed, mice were treated by a single injection of doxorubicin, with five daily injections of either vehicle or Senexin A. Results showed that Senexin A treatment strongly improved the response of A549/MEF tumors to doxorubicin [1].
Clinical trial: N/A
Reference:
[1] Donald C. Porter,Elena Farmaki,Serena Altilia et al. Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities. Proc Natl Acad Sci U S A. 2012 Aug 21; 109(34): 13799–13804.
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CDK8 Kinase Activity Promotes Glycolysis.[Pubmed:29117556]
Cell Rep. 2017 Nov 7;21(6):1495-1506.
Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancerous tissues. Despite its importance in cancer development, our understanding of mechanisms driving this form of metabolic reprogramming is incomplete. We report here an analysis of colorectal cancer cells engineered to carry a single point mutation in the active site of the Mediator-associated kinase CDK8, creating hypomorphic alleles sensitive to bulky ATP analogs. Transcriptome analysis revealed that CDK8 kinase activity is required for the expression of many components of the glycolytic cascade. CDK8 inhibition impairs glucose transporter expression, glucose uptake, glycolytic capacity and reserve, as well as cell proliferation and anchorage-independent growth, both in normoxia and hypoxia. Importantly, CDK8 impairment sensitizes cells to pharmacological glycolysis inhibition, a result reproduced with Senexin A, a dual inhibitor of CDK8/CDK19. Altogether, these results contribute to our understanding of CDK8 as an oncogene, and they justify investigations to target CDK8 in highly glycolytic tumors.
