Coenzymes,Inhibito,Enzymes,Zymogens,Substrates,Native Microorganism Creatine Amidinohydrolase
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Product Description
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Seller Information
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Description
ProductName R547 Cat No CEI-0920 Description R547 is a potent ATP-competitive inhibitor of CDK1/2/4 with Ki of 2 nM/3 nM/1 nM. It is less potent to CDK7 and GSK3α/β, while inactive to other kinases. CAS No 741713-40-6 Molecular Weight 441.45 Storage 2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO. Targets CDK IC50 80 nM Molecular Formula C18H21F2N5O4S Chemical Name (4-amino-2-(1-(methylsulfonyl)piperidin-4-ylamino)pyrimidin-5-yl)(2,3-difluoro-6-methoxyphenyl)methanone Solubility DMSO 60 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL In vitro R547 identified as a diaminopyrimidine compound, which is a potent and selective ATP-competitive CDK inhibitor. R547 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. 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. R547 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. R547 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. R547 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). R547 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%). R547 is equally efficacious (TGI, 61-95%) when dosed with 40 mg/kg i.v. once weekly. These doses of R547 are not toxic and did not result in body weight loss. R547 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. R547 inhibits tumor growth up to 95% in the HCT116 human colorectal tumor xenograft model in nude mice . R547 causes significant TGI in all of the models tested when dosed orally and i.v. at or below the maximum tolerated dose. R547 inhibits phosphorylation of retinoblastoma protein in tumors at the efficacious exposures in tumor xenograft models, providing a pharmacodynamic biomarker for clinical use. R547 reported here suggests that this is a promising molecule for evaluation in the treatment of solid tumors. category Inhibitors(c1514) cas_num 741713-40-6 Basic Info-
Product Name:
[4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone(R 547)
Other Name:[4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone(R 547);R547;[4-Amino-2-[(1-methylsulfonylpiperidin-4-yl)amino]pyrimidin-5-yl](2,3-difluoro-6-methoxyphenyl)methanone;Ro 4584820;[4-aMino-2-[[1-(Methylsulfonyl)-4-piperidinyl]aMino]-5-pyriMidinyl](2;3-difluoro-6-Methoxyphenyl)-;R547(Ro 4584820);5-[(2,3-difluoro-6-Methoxyphenyl)carbonyl]-2-N-(1-Methanesulfonylpiperidin-4-yl)pyriMidine-2,4-diaMine
CAS No.:741713-40-6
Molecular Formula:C18H21F2N5O4S
InChIKeys:JRNJNYBQQYBCLE-UHFFFAOYSA-N
Molecular Weight:441.45
Exact Mass:441.12800
UNII:T61871RKRI
DSSTox ID:DTXSID30225143
NCI Thesaurus Code:C64544
Categories:
Characteristics-
PSA:
135.89000
XLogP3:3.08540
Density:1.49
Boiling Point:703.7ºC at 760 mmHg
Flash Point:379.4ºC
Refractive Index:1.62
Hazard IdentificationClassification of the substance or mixture
no data available
GHS label elements, including precautionary statements
Pictogram(s) no data available Signal word no data available
Hazard statement(s) no data available
Precautionary statement(s) Prevention no data available
Response no data available
Storage no data available
Disposal no data available
Other hazards which do not result in classification
no data available
Handling and StoragePrecautions for safe handling
Handling in a well ventilated place. Wear suitable protective clothing. Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Use non-sparking tools. Prevent fire caused by electrostatic discharge steam.
Conditions for safe storage, including any incompatibilities
Store the container tightly closed in a dry, cool and well-ventilated place. Store apart from foodstuff containers or incompatible materials.
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Seller Information
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Business Type:
Manufactory
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Main Products:
Coenzymes,Inhibito,Enzymes,Zymogens,Substrates,Native Microorganism Creatine Amidinohydrolase
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Location:
Shirley, New York 11967, USA
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Payment Terms:
TT against copy of documents,D/P
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Average lead Time:
15
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Total Annual Revenue:
$1 million-$2.5 million
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Year of Establishment:
2004
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Country Product Purchase Quantity Date Posted Post an enquiry for this product