R-547

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C18H21F2N5O4S
Molecular Weight	441.452
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(F)C(F)=C1C(=O)C2=CN=C(NC3CCN(CC3)S(C)(=O)=O)N=C2N

InChI

InChIKey=JRNJNYBQQYBCLE-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Molecular Formula	C18H21F2N5O4S
Molecular Weight	441.452
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800018924
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/17121911 | https://www.ncbi.nlm.nih.gov/pubmed/17064073

A diaminopyrimidine compound R547 is a small molecule selective ATP-competitive inhibitor of cyclin-dependent kinases CDK1, CDK2 and CDK4 and has excellent in vitro cellular potency, inhibiting the growth of various human tumor cell lines. In vivo, R547 showed antitumor activity in all of the models tested to date, including six human tumor xenografts and an orthotopic syngeneic rat model. R547 was being developed by Roche for the treatment of solid tumours. The compound was undergoing clinical development in the US. However, no recent development has been reported and it is assumed to have been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase PCTAIRE-2 2 Target ID: CHEMBL5790 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	0.86 nM [IC50]
Serine/threonine-protein kinase PFTAIRE-1 2 Target ID: CHEMBL6162 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	11.0 nM [IC50]
Cyclin-dependent kinase 4 22 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	0.61 nM [IC50]
Cyclin-dependent kinase 4 22 Target ID: CHEMBL331 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17121911 \| https://www.ncbi.nlm.nih.gov/pubmed/17064073	Inhibitor 8297	1.0 nM [Ki]
Cyclin-dependent kinase 2 22 Target ID: CHEMBL301 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17121911 \| https://www.ncbi.nlm.nih.gov/pubmed/17064073	Inhibitor 8297	3.0 nM [Ki]
Cyclin-dependent kinase 1 27 Target ID: CHEMBL308 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17121911 \| https://www.ncbi.nlm.nih.gov/pubmed/17064073	Inhibitor 8297	2.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: http://adisinsight.springer.com/drugs/800018924	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7310 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2700 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
4152 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
8169 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.39 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	10 mg/kg single, intravenous dose: 10 mg/kg route of administration: Intravenous experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN
2.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17064073	100 mg/kg single, oral dose: 100 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		R-547 plasma	Mus musculus population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111098	https://www.001chemical.com/chem/search?q=DY111098
1PlusChem LLC	1P00FCHL	https://www.1pchem.com/search?query=1P00FCHL
AK Scientific	Y0369	https://aksci.com/item_detail.php?cat=Y0369
Aceschem	ACF019914	https://www.aceschem.com/catalog/search.do?q=ACF019914
ApexBio Technology	A8642	https://www.apexbt.com/catalogsearch/result/?q=A8642
AstaTech	77056	http://astatechinc.com/CPSResult.php?CRNO=77056
Axon MedChem	1983	https://www.axonmedchem.com/product/1983
BLD Pharm	BD316952	http://www.bldpharm.com/search/Search.html?keyword=BD316952
BOC Sciences	741713-40-6	http://www.bocsci.com/description.asp?cas=741713-40-6
BioSynth	J-502762	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-502762
Capot Chemical	34033	https://www.capotchem.com/search.do?q=34033
Cayman Chemical	17905	http://www.caymanchem.com/app/template/Product.vm/catalog/17905
Chem Scene	CS-0022	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0022
ChemShuttle	102211	https://www.chemshuttle.com/catalogsearch/result/?q=102211
Combi-Blocks	QK-4820	http://www.combi-blocks.com/cgi-bin/find.cgi?QK-4820
Excenen	EX-A105	http://www.excenen.com/searchresultlist.php?id=EX-A105
Hairui	HR33065	http://www.hairuichem.com/en/product/search.do?q=HR33065
Lab Seeker	SC-50711	http://www.labseeker.com/search.php?keywords=SC-50711&category=0
LabSeeker	SC-50711	http://www.labseeker.com/search.php?keywords=SC-50711&category=0
Matrix Scientific	144181	http://www.matrixscientific.com/144181.html
MedChem Express	HY-10014	https://www.medchemexpress.com/search.html?q=HY-10014&ft=&fa=&fp=
MolPort	MolPort-023-293-529	https://www.molport.com/shop/molecule-link/MolPort-023-293-529
Molcore	MC111098	http://www.molcore.com/CatMC111098.html
Molnova	M15831	https://www.molnova.com/en/serch-list.html?keywords=M15831
MuseChem	I008960	https://www.musechem.com/product/I008960.html
Ryan Scientific	101-93979	https://ryansci.com/products?q=101-93979&list_q=&search_type=exact
Selleck Chemicals	S2688	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2688
ShangHai Biochempartner	BCP000468	http://www.biochempartner.com/search_BCP000468
ShangHai Biochempartner	BCP02856	http://www.biochempartner.com/search_BCP02856
eMolecules	36518033	https://orderbb.emolecules.com/search/#?query=36518033
eNovation Chemicals	D210849	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D210849&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6391106045	https://mcule.com/MCULE-6391106045/

PubMed

Title	Date	PubMed
Preclinical biomarkers for a cyclin-dependent kinase inhibitor translate to candidate pharmacodynamic biomarkers in phase I patients.	2009 Sep	19755512

Patents

Sample Use Guides

In Vivo Use Guide

R 547, ranging from 8.6-195 mg/m2, is administered via a 90 min infusion on days 1 and 8, on a 21 day cycle; six patients remain in the study. In one patient with metastatic squamous skin cancer in the 155 mg/m2 cohort, tumour regression in non-target lesions was observed.

Route of Administration: Intravenous

In Vitro Use Guide

R547 inhibits the growth of various human tumor cell lines including an HCT116 cell line (IC(50) = 0.08 uM)

Substance Class	Chemical Created by `admin` on `Sat Dec 16 02:14:34 UTC 2023` Edited by `admin` on `Sat Dec 16 02:14:34 UTC 2023`
Record UNII	T61871RKRI
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

R-547

Common Name

English

RO4584820

Code

English

RO-4584820

Common Name

English

RG-547

Code

English

R 547

Code

English

RO 4584820 [WHO-DD]

Common Name

English

(4-AMINO-2-((1-METHYLSULFONYLPIPERIDIN-4-YL)AMINO)PYRIMIDIN-5-YL)(2,3-DIFLUORO-6-METHOXYPHENYL)METHANONE

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID30225143