Name: R547
Brand: Selleck Chemicals
SKU: S2688
Availability: InStock
Rating: 5 (6 reviews)

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Quality Control

Batch: Purity: 99.03%

99.03

Related Targets	HSP PD-1/PD-L1 ROCK Wee1 DNA/RNA Synthesis Microtubule Associated Ras KRas Aurora Kinase Casein Kinase
Other CDK Inhibitors	AS2863619 Ro-3306 SEL120 (SEL120-34A) hydrochloride INX-315 Tagtociclib (PF-07104091) PF-07220060 (CDK4/6-IN-6) AZD4573 ON123300 Enitociclib (BAY 1251152) Samuraciclib (ICEC0942) hydrochloride

Solubility

In vitro
Batch:

DMSO : 88 mg/mL (199.34 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
Mass value Mass unit	Concentration value Concentration unit	Volume value Volume unit	Molecular weight (g/mol)

Dilution Calculator Molecular Weight Calculator

In vivo batch selection In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	1% hydroxyethyl cellulose 1 0.2% Tween 80 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (22.65mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 1% hydroxyethyl cellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg

Average weight of animals: g

Dosing volume per animal: μL

Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO

%

% Tween 80

% ddH₂O

% DMSO

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%

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Chemical Information, Storage & Stability

Molecular Weight	441.45	Formula	C₁₈H₂₁F₂N₅O₄S	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	741713-40-6	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	Ro 4584820			Smiles	COC1=C(C(=C(C=C1)F)F)C(=O)C2=CN=C(N=C2N)NC3CCN(CC3)S(=O)(=O)C

Mechanism of Action

Targets/IC₅₀/Ki	CDK4/CyclinD1 (Cell-free assay) 1 nM(Ki) CDK1/CyclinB (Cell-free assay) 2 nM(Ki) CDK2/CyclinE (Cell-free assay) 3 nM(Ki)
In vitro	R547 identified as a diaminopyrimidine compound, which is a potent and selective ATP-competitive CDK inhibitor. This compound effectively inhibits CDK1/cyclinB, CDK2/cyclinE, and CDK4/cyclinD1(Ki=1-3nM) and is inactive(Ki>5,000nM) against a panel of >120 unrelated kinases. It 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. This chemical reduces phosphorylation of the cellular retinoblastoma protein at specific CDK phosphorylation sites at the same concentrations that induced cell cycle arrest, suggesting a potential pharmaco dynamics marker for clinical use. It inhibits the proliferation of tumor cell lines and is active in all 19 cell lines tested irrespective of tissue of origin, multidrug resistance (MDR), p53, or retinoblastoma status. This inhibitor possessing both 5-and 6-fluoro substitution culminated in an Inhibitor with low, single-digit nanomolar potency against the CDKs(Ki=0.001,0.003,and 0.001 μM for CDK1,CDK2, and CDK4,respectively) and excellent cellular potency (IC50=0.08 μM,HCT116 cell line).
In vivo	R547 administered with oral and i.v. dosing in multiple established human tumor significantly inhibits tumor activity(P < 0.01). This compound administered orally at dose of 40 mg/kg daily in colon, lung, breast, prostate, and melanoma human tumor xenograft models shows significant TGI (79-99%). It is equally efficacious (TGI, 61-95%) when dosed with 40 mg/kg i.v. once weekly. These doses of this chemical are not toxic and did not result in body weight loss. It does not show signs of overt toxicity during the course of the 3-week study and any gross pathology at necropsies done at the end of the studies. This compound inhibits tumor growth up to 95% in the HCT116 human colorectal tumor xenograft model in nude mice . It causes significant TGI in all of the models tested when dosed orally and i.v. at or below the maximum tolerated dose. It inhibits phosphorylation of retinoblastoma protein in tumors at the efficacious exposures in tumor xenograft models, providing a pharmacodynamic biomarker for clinical use. This molecule reported here suggests that this is a promising molecule for evaluation in the treatment of solid tumors.
References	[1] https://pubmed.ncbi.nlm.nih.gov/17121911/ [2] https://pubmed.ncbi.nlm.nih.gov/17064073/ [3] https://pubmed.ncbi.nlm.nih.gov/19755512/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00400296	Completed	Neoplasms	Hoffmann-La Roche	May 2005	Phase 1

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R547 CDK inhibitor

Chemical Structure

Molecular Weight: 441.45