R547 | CAS#741713-40-6 | 869369-26-6 | CDK inhibitor

MedKoo Cat#: 202420 | Name: R547

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

R547 is orally bioavailable diaminopyrimidine cyclin-dependent kinase inhibitor (CDKI) with potential antineoplastic activity. CDKI R547 selectively binds to and inhibits CDKs, especially CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1. The inhibition of CDKs results in cell cycle arrest, inhibition of tumor cell proliferation, and induction of apoptosis. Through CDK inhibition, this agent also reduces phosphorylation of the retinoblastoma (Rb) protein, thus preventing activation of transcription factor E2F and so further suppressing tumor cell proliferation. CDKs are ATP-dependent serine/threonine kinases that are important regulators of cell cycle progression and are frequently overexpressed in tumor cells.

Chemical Structure

R547

CAS#741713-40-6 (free base)

Theoretical Analysis

MedKoo Cat#: 202420

Name: R547

CAS#: 741713-40-6 (free base)

Chemical Formula: C18H21F2N5O4S

Exact Mass: 441.1282

Molecular Weight: 441.45

Elemental Analysis: C, 48.97; H, 4.79; F, 8.61; N, 15.86; O, 14.50; S, 7.26

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 225.00	2 weeks
25mg	USD 695.00	2 weeks

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Related CAS #

869369-26-6 (mesylate) 741713-40-6 (free base)

Synonym

R547; R 547; R-547; Ro4584820; Ro-4584820; Ro 4584820.

IUPAC/Chemical Name

(4-amino-2-((1-(methylsulfonyl)piperidin-4-yl)amino)pyrimidin-5-yl)(2,3-difluoro-6-methoxyphenyl)methanone

InChi Key

JRNJNYBQQYBCLE-UHFFFAOYSA-N

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)

SMILES Code

O=C(C1=CN=C(NC2CCN(S(=O)(C)=O)CC2)N=C1N)C3=C(OC)C=CC(F)=C3F

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

R547 selectively binds to and inhibits CDKs, especially CDK1/cyclin B, CDK2/cyclin E, and CDK4/cyclin D1. The inhibition of CDKs results in cell cycle arrest, inhibition of tumor cell proliferation, and induction of apoptosis. Through CDK inhibition, this agent also reduces phosphorylation of the retinoblastoma (Rb) protein, thus preventing activation of transcription factor E2F and so further suppressing tumor cell proliferation.

In vitro activity:

This study indicates that R547 has an apoptotic effect on H-4-II-E cells in 24 h. The apoptosis morphology at 24 h of treatment was clearly observed with microscopic examinations. According to their results, R547 has antiproliferative action when compared to cisplatin. Reference: Turk J Biol. 2020 Feb 17;44(1):24-33. https://pubmed.ncbi.nlm.nih.gov/32123493/

In vivo activity:

R547 showed antitumor activity in six human tumor xenografts and an orthotopic syngeneic rat model. The selective kinase inhibition profile and the preclinical antitumor activity of R547 suggest that it may be promising for development for use in the treatment of solid tumors. As of 2006, R547 was being evaluated in phase I clinical trials. Reference: Mol Cancer Ther. 2006 Nov;5(11):2644-58. https://pubmed.ncbi.nlm.nih.gov/17121911/

	Solvent	mg/mL	mM
Solubility
	DMSO	60.0	135.92

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 441.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Hacioğlu B, Kuş G, Kutlu HM, Kabadere S. The effect of R547, a cyclin-dependent kinase inhibitor, on hepatocellular carcinoma cell death. Turk J Biol. 2020 Feb 17;44(1):24-33. doi: 10.3906/biy-1907-3. PMID: 32123493; PMCID: PMC7049457. 2. Sorf A, Novotna E, Hofman J, Morell A, Staud F, Wsol V, Ceckova M. Cyclin-dependent kinase inhibitors AZD5438 and R547 show potential for enhancing efficacy of daunorubicin-based anticancer therapy: Interaction with carbonyl-reducing enzymes and ABC transporters. Biochem Pharmacol. 2019 May;163:290-298. doi: 10.1016/j.bcp.2019.02.035. Epub 2019 Feb 28. PMID: 30826329. 3. DePinto W, Chu XJ, Yin X, Smith M, Packman K, Goelzer P, Lovey A, Chen Y, Qian H, Hamid R, Xiang Q, Tovar C, Blain R, Nevins T, Higgins B, Luistro L, Kolinsky K, Felix B, Hussain S, Heimbrook D. In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther. 2006 Nov;5(11):2644-58. doi: 10.1158/1535-7163.MCT-06-0355. PMID: 17121911. 4. 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. doi: 10.1021/jm0606138. PMID: 17064073.

In vitro protocol:

In vivo protocol:

1. DePinto W, Chu XJ, Yin X, Smith M, Packman K, Goelzer P, Lovey A, Chen Y, Qian H, Hamid R, Xiang Q, Tovar C, Blain R, Nevins T, Higgins B, Luistro L, Kolinsky K, Felix B, Hussain S, Heimbrook D. In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther. 2006 Nov;5(11):2644-58. doi: 10.1158/1535-7163.MCT-06-0355. PMID: 17121911. 2. 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. doi: 10.1021/jm0606138. PMID: 17064073.

1: Sawant RR, Jhaveri AM, Koshkaryev A, Zhu L, Qureshi F, Torchilin VP. Targeted transferrin-modified polymeric micelles: enhanced efficacy in vitro and in vivo in ovarian carcinoma. Mol Pharm. 2014 Feb 3;11(2):375-81. doi: 10.1021/mp300633f. Epub 2013 Dec 19. PubMed PMID: 24325630. 2: 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. doi: 10.1186/1752-0509-6-54. PubMed PMID: 22651900; PubMed Central PMCID: PMC3433335. 3: Sangwan M, McCurdy SR, Livne-Bar I, Ahmad M, Wrana JL, Chen D, Bremner R. Established and new mouse models reveal E2f1 and Cdk2 dependency of retinoblastoma, and expose effective strategies to block tumor initiation. Oncogene. 2012 Nov 29;31(48):5019-28. doi: 10.1038/onc.2011.654. Epub 2012 Jan 30. PubMed PMID: 22286767. 4: Cohen-Solal KA, Merrigan KT, Chan JL, Goydos JS, Chen W, Foran DJ, Liu F, Lasfar A, Reiss M. Constitutive Smad linker phosphorylation in melanoma: a mechanism of resistance to transforming growth factor-β-mediated growth inhibition. Pigment Cell Melanoma Res. 2011 Jun;24(3):512-24. doi: 10.1111/j.1755-148X.2011.00858.x. Epub 2011 Apr 28. PubMed PMID: 21477078; PubMed Central PMCID: PMC3108265. 5: DePinto W, Chu XJ, Yin X, Smith M, Packman K, Goelzer P, Lovey A, Chen Y, Qian H, Hamid R, Xiang Q, Tovar C, Blain R, Nevins T, Higgins B, Luistro L, Kolinsky K, Felix B, Hussain S, Heimbrook D. In vitro and in vivo activity of R547: a potent and selective cyclin-dependent kinase inhibitor currently in phase I clinical trials. Mol Cancer Ther. 2006 Nov;5(11):2644-58. PubMed PMID: 17121911. 6: 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. PubMed PMID: 17064073.