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Purity: ≥98%
R547 (R-547; Ro4584820; R 547; Ro-4584820) is a potent, selective and ATP-competitive inhibitor of CDK1/2/4 with potential antitumor activity. R547 exhibits lower potency or inactivity against CDK7, GSK3α/β, and additional kinases. R547 is effective against all 19 cell lines tested, regardless of tissue of origin, multidrug resistance (MDR), p53, or retinoblastoma status. It also inhibits the proliferation of tumor cell lines. An inhibitor with low, single-digit nanomolar potency against the CDKs and excellent cellular potency (IC50=0.08 μM, HCT116 cell line) was produced by R547, which possessed both 5- and 6-fluoro substitution.
| Targets |
Cdk1/cyclin B (Ki = 2 nM); CDK2/cyclinE (Ki = 3 nM); CDK4/cyclin D (Ki = 1 nM); cdk2/cyclin A (IC50 = 0.1 nM); CDK2/cyclinE (IC50 = 0.4 nM); Cdk1/cyclin B (IC50 = 0.2 nM); CDK3/Cyclin E (IC50 = 0.8 nM); CDK5/p35 (IC50 = 0.1 nM); cdk6/cyclin D3 (IC50 = 4 nM); CDK7/cyclin H (IC50 = 171 nM); GSK-3α (IC50 = 46 nM); GSK-3β (IC50 = 260 nM)
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| Enzyme Assay |
R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM.
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| Cell Assay |
R547 is inactive (Ki>5,000nM) against a panel of more than 120 unrelated kinases, but it effectively inhibits CDK1/cyclinB, CDK2/cyclinE, and CDK4/cyclinD1 (Ki=1-3nM). With IC50s<0.60 μM, R547 potently suppresses tumor cell line proliferation, regardless of p53 status, histologic type, retinoblastoma protein, or multidrug resistance. At the same concentrations that cause cell cycle arrest, R547 decreases the phosphorylation of the cellular retinoblastoma protein at particular CDK phosphorylation sites, indicating that it may be a useful pharmacodynamic marker for clinical applications. R547 is effective against all 19 cell lines tested and inhibits the growth of tumor cell lines, regardless of the tissue of origin, p53, multidrug resistance (MDR), or retinoblastoma status. The combination of 5- and 6-fluoro substitution in R547 resulted in an inhibitor with excellent cellular potency (IC50=0.08 μM, HCT116 cell line) and low, single-digit nanomolar potency against the CDKs (Ki=0.001,0.003, and 0.001 μM for CDK1, CDK2, and CDK4, respectively).
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| References |
| Molecular Formula |
C18H21F2N5O4S
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| Molecular Weight |
441.45
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| Exact Mass |
441.13
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| Elemental Analysis |
C, 48.97; H, 4.79; F, 8.61; N, 15.86; O, 14.50; S, 7.26
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| CAS # |
741713-40-6
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| Related CAS # |
869369-26-6 (mesylate);741713-40-6;
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| Appearance |
Solid powder
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| SMILES |
COC1=C(C(=C(C=C1)F)F)C(=O)C2=CN=C(N=C2N)NC3CCN(CC3)S(=O)(=O)C
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| InChi Key |
JRNJNYBQQYBCLE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H21F2N5O4S/c1-29-13-4-3-12(19)15(20)14(13)16(26)11-9-22-18(24-17(11)21)23-10-5-7-25(8-6-10)30(2,27)28/h3-4,9-10H,5-8H2,1-2H3,(H3,21,22,23,24)
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| Chemical Name |
[4-amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl]-(2,3-difluoro-6-methoxyphenyl)methanone
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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) |
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| Preparing Stock Solutions | 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 |
*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 |
| NCT00400296 | Completed | Drug: RG547 | Neoplasms | Hoffmann-La Roche | May 2005 | Phase 1 |
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