Cat. No.: HY-10014

R547

2 Cited Publications

Customer Review

Based on 2 publication(s) in Google Scholar

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.

For research use only. We do not sell to patients.

Purity: 99.57%
CAS No.: 741713-40-6
Formula: C₁₈H₂₁F₂N₅O₄S
Molecular Weight:441.45

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

R547 Chemical Structure

CAS No.: 741713-40-6

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (2)
Purity & Documentation
References
Calculators
Help & FAQs
Bioz

Biological Activity

Description

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].

IC₅₀ & Target^[1]

Cdk1/cyclin B

2 nM (Ki)

CDK2/cyclinE

3 nM (Ki)

CDK4/cyclin D

1 nM (Ki)

cdk2/cyclin A

0.1 nM (IC₅₀)

CDK2/cyclinE

0.4 nM (IC₅₀)

Cdk1/cyclin B

0.2 nM (IC₅₀)

CDK3/Cyclin E

0.8 nM (IC₅₀)

CDK5/p35

0.1 nM (IC₅₀)

cdk6/cyclin D3

4 nM (IC₅₀)

CDK7/cyclin H

171 nM (IC₅₀)

GSK-3α

46 nM (IC₅₀)

GSK-3β

260 nM (IC₅₀)

All CDK Isoforms :

All GSK-3 Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
HCT-116	IC₅₀	0.08 μM Compound: 39, R547	Inhibition of HCT116 cell growth Inhibition of HCT116 cell growth	[PMID: 17064073]

In Vitro

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.

Cell Cytotoxicity Assay^[4]

Cell Line:

Human tumor cell lines (MDA-MB-468, MDA-MB-435, MCF-7, HCT116, SW480, RKO, HT-29, HCT15, H460a, C33A, DU145, OSA-CL, LOX, JEKO-1, REC-1)
Concentration:

MTT assay
Incubation Time:

5 days
Result:

Has potent in vitro antiproliferative activity.

Cell Cycle Analysis^[4]

Cell Line:

R547, HCT116
Concentration:

0.1 μM, 0.2 μM, 0.6 μM
Incubation Time:

20 hours
Result:

Decrease in BrdUrd incorporation and in percentage S phase in a dose-dependent, indicative of a cell cycle block in G1-S plus G2-M.

Western Blot Analysis^[4]

Cell Line:

HCT116 cells
Concentration:

0.1 μM, 0.2 μM, 0.6 μM
Incubation Time:

24 hours, 48 hours, 72 hours
Result:

Showed a band corresponding to a p48/retinoblastoma fragment that becomes more intense at 48 and 72 hours.

In Vivo

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.

Animal Model:

13-14 weeks old female immunodeficient nude mice (23-25 g), with HCT116/H460a/MDA-MB-435/DU145/LOX/A549 cells xenograft^[4]
Dosage:

40 mg/kg
Administration:

Oral administration; daily; for 3-weeks
Result:

Showed antitumor activity in all of the models in this study.

Chemical Information

CAS No. 741713-40-6
Appearance Solid
Molecular Weight 441.45
Formula C₁₈H₂₁F₂N₅O₄S
Color White to off-white
SMILES

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

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (2)

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Journal Impact Factor

Science

The target landscape of clinical kinase drugs. [Abstract]

2017 Dec 1;358(6367):eaan4368. PMID: 29191878
Cell Chem Biol

Overcoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors. [Abstract]

2018 Feb 15;25(2):135-142.e5. PMID: 29276047

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (284 KB)
SDS (480 KB)
- English - EN (480 KB)
- Français - FR (480 KB)
- Deutsch - DE (480 KB)
- Norwegian - NO (480 KB)
- Español - ES (480 KB)
- Swedish - SV (480 KB)
- Italian - IT (480 KB)
- Portuguese - PT (480 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[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]

Calculators

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Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

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R547

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Publications Citing Use of MedChemExpress (MCE) R547

All CDK Isoforms

All GSK-3 Isoforms