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].

上海金畔生物科技有限公司 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

441.45

C₁₈H₂₁F₂N₅O₄S

741713-40-6

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 50 mg/mL (113.26 mM)

* “≥” means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (5.66 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.66 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (5.66 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.66 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [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.

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

  [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.

  [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

  [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