R547 

R547 is a potent, selective and orally active ATP-competitive CDK inhibitor, with K_is of 2 nM, 3 nM and 1 nM for CDK1/cyclin B, CDK2/cyclin E and CDK4/cyclin D1, respectively^{[1][2][3][4][5]}.

R547 effectively inhibits CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1 (Ki = 1–3 nmol/L) and is inactive (Ki > 5,000 nmol/L) against a panel of >120 unrelated kinases in cell-free assays^[4].
R547 effectively inhibits the proliferation of tumor cell lines independent of multidrug resistant status, histologic type, retinoblastoma protein, or p53 status, with IC₅₀s <0.60 μM^[4].
R547 reduces phosphorylation of the cellular retinoblastoma protein at specific CDK phosphorylation sites at the same concentrations that induced cell cycle arrest^[4].
R547 has anti-proliferative activity in tumor cells independent of p53, retinoblastoma, or MDR status^[4].
R547 blocks tumor cells in G1 plus G2 and induces apoptosis^[4].
R547 induces apoptosis as measured by DNA fragmentation^[4].
R547 inhibits phosphorylation of retinoblastoma protein in humantumor cells^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

R547 has significant in vivo efficacy with daily oral and once weekly i.v. dosing^[4].
R547 inhibits phosphorylation of retinoblastoma protein in tumors^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

441.45

C₁₈H₂₁F₂N₅O₄S

741713-40-6

Solid

White to off-white

O=S(N1CCC(NC2=NC(N)=C(C(C3=C(C(F)=CC=C3OC)F)=O)C=N2)CC1)(C)=O

Room temperature in continental US; may vary elsewhere.

• [1]. Chu XJ, DePinto W, Bartkovitz D, So SS, Vu BT, Packman K, Lukacs C, Ding Q, Jiang N, Wang K, Goelzer P, Yin X, Smith MA, Higgins BX, Chen Y, Xiang Q, Moliterni J, Kaplan G, Graves B, Lovey A, Fotouhi N.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.J Med Chem. 2006 Nov 2;49(22):6549-60.  [Content Brief]

  [2]. Bayés M, Rabasseda X, Prous JR.Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2007 Jul-Aug;29(6):427-37.  [Content Brief]

  [3]. Martin F, Thomson TM, Sewer A, Drubin DA, Mathis C, Weisensee D, Pratt D, Hoeng J, Peitsch MC.Assessment of network perturbation amplitudes by applying high-throughput data to causal biological networks.BMC Syst Biol. 2012 May 31;6:54.  [Content Brief]

  [4]. DePinto, Wanda et al In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials Molecular Cancer Therapeutics (2006), 5(11), 2644-2658  [Content Brief]

  [5]. Jones, Clifford D.; Andrews, David M. Imidazole pyrimidine amides as potent, orally bioavailable cyclin-dependent kinase inhibitors Bioorganic & Medicinal Chemistry Letters (2008), 18(24), 6486-6489  [Content Brief]