Antibodies
CYC116
- 貨號 Cat. No.
- S1171
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
CYC116
CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1.
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
Biological Activity
| Description | CYC116 is a potent inhibitor of Aurora A/B with Ki of 8.0 nM/9.2 nM, is less potent to VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, not active against PKA, Akt/PKB, PKC, no effect on GSK-3α/β, CK2, Plk1 and SAPK2A. Phase 1. | |||||
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| Targets | Aurora A/B | VEGFR | ||||
| IC50 | 8.0 nM/9.2 nM (Ki) | 44 nM (Ki) [1] | ||||
| In vitro | The most Aurora-selective CYC116 shows inhibitory effect on Aurora A and B kinases 50-fold more potently than any of the CDKs assayed. [1] CYC116 is initially screened against a panel of human leukemia and solid tumor cell lines using an MTT antiproliferative assay. The results show that CYC116 has broad-spectrum antitumor activity and shows specific cytotoxicity against the acute myelogenous leukemia cell line MV4-11 with IC50 of 34 nM. [1] In addition, anti-proliferative activity of CYC116 is found to be associated with Aurora A and B modulation such as, inhibition of Aurora autophosphorylation, reduction of histone H3 phosphorylation, polyploidy, followed by cell death, resulting from a failure in cytokinesis. [1] | |||||
| In vivo | Mice bearing subcutaneous NCI-H460 xenografts are given CYC116 orally for 5 days, at dose levels of 75 and 100 mg/kg q.d. It leads to tumor growth delays of 2.3 and 5.8 days, which translated into specific growth delays of 0.32 and 0.81, respectively. [1] | |||||
| Features | An orally bioavailable, small molecule inhibitor of Aurora kinase/VEGFR2. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| Kinase Assays | Aurora A kinase assays are performed using a 25 μL reaction volume (25 mM β-glycerophosphate, 20 mM Tris/HCl, pH 7.5, 5 mM EGTA, 1 mM DTT, 1 mM Na3VO4, 10 μg of kemptide (peptide substrate)). Recombinant Aurora A kinase is diluted in 20 mM Tris/HCl, pH 8, containing 0.5 mg/mL BSA, 2.5% glycerol, and 0.006% Brij-35. Reactions are started by the addition of 5 μL Mg/ATP mix (15 mM MgCl2, 100 μM ATP, with 18.5 kBq γ-32P-ATP per well) and incubated at 30°C for 30 minutes before termination with 25 μL of 75 mM H3PO4. Aurora B kinase assays are performed like Aurora A except that prior to use, Aurora B is activated in a separate reaction at 30°C for 60 minutes with inner centromere protein. |
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Cell Assay:
| Cell lines | HeLa, MCF7, MV4-11 and A2780 cells |
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| Concentrations | 0-10 μM |
| Incubation Time | 72 or 96 hours |
| Method | Standard MTT assays are performed. In short, cells are seeded into 96-well plates according to doubling time and incubated overnight at 37°C. Test compounds are made up in DMSO, a 3-fold dilution series is prepared in 100 μL of cell medium, added to cells (in triplicates) and incubated for 72 or 96 hours at 37°C. MTT is made up as a stock of 5 mg/mL in cell medium, and the solution is filter-sterilized. Medium is removed from the cells followed by a wash with PBS. MTT solution is then added at 20 μL/well and incubated in the dark at 37°C for 4 hours. MTT solution is removed and cells are again washed with 200 μL of PBS. MTT dye is solubilized with 200 μL/well of DMSO by agitation. Absorbance is read at 540 nm and data analyzed using curve-fitting software to determine IC50 values. |
Animal Study:
| Animal Models | NCI-H460 cells are implanted intraperitoneally into the mice. |
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| Dosages | 75 and 100 mg/kg |
| Administration | Administered via p.o. |
| Solubility | 1% DMSO/30% polyethylene glycol/1% Tween 80, 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00560716 | Terminated | Solid Tumors | Cyclacel Pharmaceuticals, Inc. | 2007-06 | Phase 1 |
Chemical Information
| Molecular Weight (MW) | 368.46 |
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| Formula | C18H20N6OS |
| CAS No. | 693228-63-6 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | N/A |
| Solubility (25°C) * | In vitro | DMSO | 24 mg/mL heat (65 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 1% DMSO/30% polyethylene glycol/1% Tween 80, | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. | |||
| Chemical Name | 4-(2-amino-4-methylthiazol-5-yl)-N-(4-morpholinophenyl)pyrimidin-2-amine |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.36846 | 3.6846 | 7.3692 | 11.0538 |
Customer Reviews (1)
 Click to enlarge | Rating | |
| Source | CYC116 purchased from Selleck | |
| Method | Western blot | |
| Cell Lines | MDA-MB-231 cells | |
| Concentrations | 0-10 μM | |
| Incubation Time | ||
| Results | CYC116 decreased protein expression levels of Aurora and Aurora A/B/C phosphorylation in MDA-MB-231 cells. |
Product Citations (1)
Targeting Sonic Hedgehog-Associated Medulloblastoma through Inhibition of Aurora and Polo-like Kinases. [Markant SL, et al. Cancer Res 2013;73(20):6310-22]
PubMed: 24067506
