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Purity: ≥98%
CYC116 is a novel, potent, orally bioavailable inhibitor of Aurora A/B/C kinases with potential antitumor activity. It inhibits Aurora A/B/C with IC50s of 44 nM, 19 nM and 65 nM respectively. CYC116 is less potent against VEGFR2 (Ki of 44 nM), with 50-fold greater potency than CDKs, and is not active against PKA, Akt/PKB, PKC, GSK-3α/β, CK2, Plk1 and SAPK2A.
ln Vitro |
Moreover, CYC-116 suppresses FLT3, Src, Lck, and VEGFR2 at 44, 82, 280, and 44 nM, respectively. Broad-spectrum anticancer action is possible for CYC-116. With IC50s of 0.599, 0.59, 0.241, 0.34, 0.725, 1.375, 0.471, 0.034, 0.372, 0.681, 0.151, 1.626, 0.775, 0.308, 0.110, and 0.09 for MCF7, HeLa, Colo 205, HCT-116, HT29, K562, CCRF -CEM, MV4-11, HL60, NCI-H460, A2780, BxPC3, HuPT4, Mia-Paca-2, Saos-2, and Messa cells, CYC-116 exhibits strong antiproliferative activity against cancer cell lines. Histone H3 phosphorylation in HeLa cell lysates is completely inhibited after 7 hours of treatment with 1.25 μM CYC-116[1].
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ln Vivo |
Tumor growth delays of 2.3 and 5.8 days are caused by oral administration of CYC-116 at dose levels of 75 and 100 mg/kg qd, respectively. These tumor growth delays translate into specific growth delays of 0.32 and 0.81. For the duration of the trial, the mean relative tumor volumes of mice receiving CYC-116 at both dose levels are smaller than those of animals given with a vehicle. On days 6 and 9, the growth decrease is statistically significant at 100 mg/kg po qd[1].
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Animal Protocol |
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References |
[1]. Wang S, et al. Discovery of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amine aurora kinase inhibitors. J Med Chem. 2010 Jun 10;53(11):4367-78
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Molecular Formula |
C18H20N6OS
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Molecular Weight |
368.46
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CAS # |
693228-63-6
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Related CAS # |
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SMILES |
NC1=NC(C)=C(C2=NC(NC3=CC=C(N4CCOCC4)C=C3)=NC=C2)S1
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InChi Key |
GPSZYOIFQZPWEJ-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C18H20N6OS/c1-12-16(26-17(19)21-12)15-6-7-20-18(23-15)22-13-2-4-14(5-3-13)24-8-10-25-11-9-24/h2-7H,8-11H2,1H3,(H2,19,21)(H,20,22,23)
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Chemical Name |
4-methyl-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine
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Synonyms |
CYC 116; CYC-116; CYC116.
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: 1.5 mg/mL (4.07 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.5 mg/mL (4.07 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 15.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 1% DMSO+30% polyethylene glycol+1% Tween 80:30mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.7140 mL | 13.5700 mL | 27.1400 mL | |
5 mM | 0.5428 mL | 2.7140 mL | 5.4280 mL | |
10 mM | 0.2714 mL | 1.3570 mL | 2.7140 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT00560716 | Terminated | Drug: CYC116 | Solid Tumors | Cyclacel Pharmaceuticals, Inc. | June 2007 | Phase 1 |
Through cell-based screening of our kinase-directed compound collection, we discovered that a subset of N-phenyl-4-(thiazol-5-yl)pyrimidin-2-amines were potent cytotoxic agents against cancer cell lines, suppressed mitotic histone H3 phosphorylation, and caused aberrant mitotic phenotypes. It was subsequently established that these compounds were in fact potent inhibitors of aurora A and B kinases. It was shown that potency and selectivity of aurora kinase inhibition correlated with the presence of a substituent at the aniline para-position in these compounds. The anticancer effects of lead compound 4-methyl-5-(2-(4-morpholinophenylamino)pyrimidin-4-yl)thiazol-2-amine (18; Ki values of 8.0 and 9.2 nM for aurora A and B, respectively) were shown to emanate from cell death following mitotic failure and increased polyploidy as a consequence of cellular inhibition of aurora A and B kinases. Preliminary in vivo assessment showed that compound 18 was orally bioavailable and possessed anticancer activity. Compound 18 (CYC116) is currently undergoing phase I clinical evaluation in cancer patients. td> |