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R547

Cat. No. M1740
R547 Structure
Size Price Availability Quantity
Free Sample (0.5-1 mg)  USD 0 In stock
5mg USD 200 In stock
10mg USD 350 In stock
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Quality Control
Biological Activity

R547 is a potent and selective ATP-competitive CDK inhibitor.In cell-free assays, R547 effectively inhibited CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1 (Ki = 1–3 nmol/L) and was inactive (Ki > 5,000 nmol/L) against a panel of >120 unrelated kinases. In vitro, R547 effectively inhibited the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC50s ≤ 0.60 μmol/L.

Protocol
Cell Experiment
Cell lines human tumor cell lines HCT116, H460a, MDA-MB-435, DU145, LOX, and A549
Preparation method Tetrazolium Dye Proliferation [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] Assay
Concentrations 0~1 μM
Incubation time 48 h
Animal Experiment
Animal models HCT116, H460a, MDA-MB-435, DU145, LOX, and A549
Formulation Oral R547 was formulated as a suspension in Klucel LF/Tween 80, and i.v. R547 was formulated as a solution in hydroxylpropyl β-cyclodextrin, sodium hydroxide, and water for i.v. injection
Dosages 40 mg/kg daily oral dosing and 40 mg/kg i.v. once weekly
Administration oral or i.v.
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 441.45
Formula C18H21F2N5O4S
CAS Number 741713-40-6
Purity 100.00%
Solubility DMSO
Storage at -20°C
Customer Product Validations & Biological Datas
Source Oncogene (2012). Figure 6. R547
Method I.P.
Cell Lines p27−/− male mice
Concentrations 20 mg/kg
Incubation Time 13 day
Results Strikingly, R547 reduced dysplasia (Figure 6D) and also modestly reduced ectopic mitoses but had no effect on progenitor mitoses that are distant or adjacent to phalloidin-marked apical membranes, respectively
Rating
References

Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks.
Martin et al. BMC Syst Biol. 2012 May 31;6:54. PMID: 22651900.

Constitutive Smad linker phosphorylation in melanoma: a mechanism of resistance to transforming growth factor-β-mediated growth inhibition.
Cohen-Solal et al. Pigment Cell Melanoma Res. 2011 Jun;24(3):512-24. PMID: 21477078.

In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials.
DePinto et al. Mol Cancer Ther. 2006 Nov;5(11):2644-58. PMID: 17121911.

Discovery of [4-Amino-2-(1-methanesulfonylpiperidin-4-ylamino)pyrimidin-5-yl](2,3-difluoro-6- methoxyphenyl)methanone (R547), a potent and selective cyclin-dependent kinase inhibitor with significant in vivo antitumor activity.
Chu et al. J Med Chem. 2006 Nov 2;49(22):6549-60. PMID: 17064073.

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: R547 supplier, CDK, inhibitors

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