R547 (Synonyms: Ro 4584820) |
Catalog No.GC17400 |
CDK1/2/4 inhibitor,ATP-competitive
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 741713-40-6
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
R547 is a novel, selective inhibitor of cell cycle and transcriptional cyclin dependent kinases with a Ki of median 2 nM for CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1((Ki=0.001,0.003,and 0.001 μM for CDK1,CDK2, and CDK4,respectively).[1]
Cyclin-dependent kinases (CDKs) are a family of protein kinases regulating the cell cycle, transcription, mRNA processing, and the differentiation of nerve cells which considered a potential anticancer target. CDK inhibitors such as Seliciclib are undergoing clinical trials. Although it was originally developed as a potential anti-cancer drug, in recent laboratory tests Seliciclib has also proven to induce apoptosis in neutrophil granulocytes, which mediate inflammation.[2].
R547 inhibited the proliferation of tumor cell lines and is active in all 19 cell lines tested irrespective of tissue of origin, multidrug resistance (MDR), p53, or retinoblastoma status. R547 possessing both 5-and 6-fluoro substitution culminated in an Inhibitor with low, single-digit nanomolar potency against the CDKs and excellent cellular potency (IC50=0.08 μM,HCT116 cell line). R547 administered orally at dose of 40 mg/kg daily in colon, lung, breast, prostate, and melanoma human tumor xenograft models shows significant TGI (79-99%). R547 is equally efficacious (TGI, 61-95%) when dosed with 40 mg/kg i.v. once weekly. These doses of R547 are not toxic and did not result in body weight loss. R547 does not show signs of overt toxicity during the course of the 3-week study and any gross pathology at necropsies done at the end of the studies. [3]R547 inhibits tumor growth up to 95% in the HCT116 human colorectal tumor xenograft model in nude mice . R547 causes significant TGI in all of the models tested when dosed orally and i.v. at or below the maximum tolerated dose. R547 inhibits phosphorylation of retinoblastoma protein in tumors at the efficacious exposures in tumor xenograft models, providing a pharmacodynamic biomarker for clinical use. R547 reported here suggests that this is a promising molecule for evaluation in the treatment of solid tumors. [4]
References:
1. Davis MI1, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. “Comprehensive analysis of kinase inhibitor selectivity.” Nat Biotechnol. 2011, 29(11):1046-51.
2. Rossi, Adriano G. “Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis.” 2006. Nature Medicine 12 .
3. Rodriguez A , et al. Mol Cancer Ther, 2006, 5(11), 2644-2658.
4. Chu XJ, et al. J Med Chem, 2006, 49(22), 6549-6560.
Cas No. | 741713-40-6 | SDF | |
Synonyms | Ro 4584820 | ||
Chemical Name | [4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone | ||
Canonical SMILES | COC1=C(C(=C(C=C1)F)F)C(=O)C2=CN=C(N=C2N)NC3CCN(CC3)S(=O)(=O)C | ||
Formula | C18H21F2N5O4S | M.Wt | 441.45 |
Solubility | DMF: 15mg/ml,DMSO: 15 mg/ml,DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml | 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. |
||
Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. |
Prepare stock solution | |||
1 mg | 5 mg | 10 mg | |
1 mM | 2.2653 mL | 11.3263 mL | 22.6526 mL |
5 mM | 0.4531 mL | 2.2653 mL | 4.5305 mL |
10 mM | 0.2265 mL | 1.1326 mL | 2.2653 mL |
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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.
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