REFAMETINIB

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H20F3IN2O5S
Molecular Weight	572.337
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(NS(=O)(=O)C2(C[C@H](O)CO)CC2)C(NC3=CC=C(I)C=C3F)=C(F)C(F)=C1

InChI

InChIKey=RDSACQWTXKSHJT-NSHDSACASA-N

InChI=1S/C19H20F3IN2O5S/c1-30-15-7-13(21)16(22)18(24-14-3-2-10(23)6-12(14)20)17(15)25-31(28,29)19(4-5-19)8-11(27)9-26/h2-3,6-7,11,24-27H,4-5,8-9H2,1H3/t11-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C19H20F3IN2O5S
Molecular Weight	572.337
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800027148
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19706763

Refametinib (RDEA-119, BAY- 869766) is a highly potent and selective inhibitor of mitogen-activated ERK kinase (MEK1/2) activity, Refametinib binds to an allosteric pocket adjacent to the ATP binding site, locking the enzyme in a catalytically inactive conformation. This compound is highly efficacious at inhibiting cell proliferation in several tumor cell lines in vitro. In vivo, Refametinib exhibits potent activity in xenograft models of cancers. Ardea Biosciences (a subsidiary of AstraZeneca) and Bayer HealthCare are developing refametinib for the treatment of cancer. The sulfonamide agent was originally developed by Valeant Pharmaceuticals International. Refametinib is in phase II development for hepatocellular carcinoma, and phase I/II development for pancreatic cancer and other solid tumours.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Dual specificity mitogen-activated protein kinase kinase 1 20 Target ID: CHEMBL3587 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19706763	Inhibitor 8504		19.0 nM [IC50]
Dual specificity mitogen-activated protein kinase kinase 2 10 Target ID: CHEMBL2964 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19706763	Inhibitor 8504		47.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hepatocellular carcinoma 83 Sources: http://adisinsight.springer.com/drugs/800027148	Primary		Phase II 1147	Unknown Approved Use Unknown
Pancreatic cancer 98 Sources: http://adisinsight.springer.com/drugs/800027148	Primary		Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1046 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1442 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
9758 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
17975 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
10.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/23434733	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		REFAMETINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.2% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19706763			REFAMETINIB plasma	Homo sapiens

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GRTC	https://www.1pchem.com/search?query=1P00GRTC
AChemBlock	O32834	http://www.achemblock.com/catalogsearch/result/?q=O32834
AK Scientific	2254AH	https://aksci.com/item_detail.php?cat=2254AH
AK Scientific	SYN5691	https://aksci.com/item_detail.php?cat=SYN5691
ApexBio Technology	B1267	https://www.apexbt.com/catalogsearch/result/?q=B1267
AstaTech	F51934	http://astatechinc.com/CPSResult.php?CRNO=F51934
BLD Pharm	BD631011	http://www.bldpharm.com/search/Search.html?keyword=BD631011
BOC Sciences	923032-37-5	http://www.bocsci.com/description.asp?cas=923032-37-5
Cayman Chemical	16997	http://www.caymanchem.com/app/template/Product.vm/catalog/16997
Chem Scene	CS-1818	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1818
ChemShuttle	140546	https://www.chemshuttle.com/catalogsearch/result/?q=140546
eMolecules	300565832	https://orderbb.emolecules.com/search/#?query=300565832
eMolecules	37153223	https://orderbb.emolecules.com/search/#?query=37153223
eMolecules	44816744	https://orderbb.emolecules.com/search/#?query=44816744
eNovation Chemicals	D395269	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D395269&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A2481	http://www.excenen.com/searchresultlist.php?id=EX-A2481
Hairui	HR109724	http://www.hairuichem.com/en/product/search.do?q=HR109724
KeyOrganics	AS-16994	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16994
mcule	MCULE-2005618157	https://mcule.com/MCULE-2005618157/
mcule	MCULE-5702269108	https://mcule.com/MCULE-5702269108/
mcule	MCULE-9106608516	https://mcule.com/MCULE-9106608516/
MedChem Express	HY-14691	https://www.medchemexpress.com/search.html?q=HY-14691&ft=&fa=&fp=
Molnova	M16609	https://www.molnova.com/en/serch-list.html?keywords=M16609
Molnova	M16610	https://www.molnova.com/en/serch-list.html?keywords=M16610
MolPort	MolPort-023-293-525	https://www.molport.com/shop/molecule-link/MolPort-023-293-525
MuseChem	I005488	https://www.musechem.com/product/I005488.html
TargetMol	T6636	https://www.targetmol.com/search?keyword=T6636

PubMed

Title	Date	PubMed
Allosteric MEK1/2 inhibitor refametinib (BAY 86-9766) in combination with sorafenib exhibits antitumor activity in preclinical murine and rat models of hepatocellular carcinoma.	2013-10	24204195
MEK and the inhibitors: from bench to bedside.	2013-04-12	23587417
Multicenter phase I trial of the mitogen-activated protein kinase 1/2 inhibitor BAY 86-9766 in patients with advanced cancer.	2013-03-01	23434733
RDEA119/BAY 869766: a potent, selective, allosteric inhibitor of MEK1/2 for the treatment of cancer.	2009-09-01	19706763

Patents

Sample Use Guides

In Vivo Use Guide

Refametinib (RDEA-119, BAY- 869766) was administered orally daily in 28-day courses, with doses escalated to establish the maximum-tolerated dose (MTD). The MTD was 100 mg given once-daily or in two divided doses. The drug was well-tolerated, with good oral absorption, dose proportional pharmacokinetics, target inhibition at the MTD, and some evidence of clinical benefit across a range of tumor types.

Route of Administration: Oral

In Vitro Use Guide

Refametinib (RDEA-119, BAY- 869766) potently inhibited MEK activity as measured by phosphorylation of ERK1/2 across several human cancer cell lines of different tissue origins and BRAF mutational status with EC50 values ranging from 2.5 to 15.8 nM. RDEA119 inhibited anchorage-dependent growth of human cancer cell lines harboring the gain-of-function V600E BRAF mutant with GI50 values ranging from 67 to 89 nM. In contrast, RDEA119 had significantly less growth-inhibitory potency against cell lines with wild-type BRAF (A431 cells) or MDA-MB-231 cells harboring a BRAF mutation G464V that shows minimal (<2-fold increase) enhancement of inherent kinase activity. Interestingly, under anchorage-independent conditions, GI50 values for all cell lines tested were similar 40–84 nM.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:35:53 GMT 2025` Edited by `admin` on `Wed Apr 02 09:35:53 GMT 2025`
Record UNII	JPX07AFM0N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

REFAMETINIB

Official Name

English

BAY-869766

Preferred Name

English

BAY869766

Code

English

BAY86-9766

Code

English

BAY-8697661

Code

English

CYCLOPROPANESULFONAMIDE, N-(3,4-DIFLUORO-2-((2-FLUORO-4-IODOPHENYL)AMINO)-6-METHOXYPHENYL)-1-((2S)-2,3-DIHYDROXYPROPYL0-

Common Name

English

RDEA-119

Code

English

Refametinib [WHO-DD]

Common Name

English

BAY8697661

Code

English

RDEA119

Code

English

BAY-86-9766

Code

English

refametinib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C129825