AGERAFENIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H22F3N5O5
Molecular Weight	517.4572
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC2=C(C=C1OC)C(OC3=CC(NC(=O)NC4=NOC(=C4)C(C)(C)C(F)(F)F)=CC=C3)=NC=N2

InChI

InChIKey=DKNUPRMJNUQNHR-UHFFFAOYSA-N

InChI=1S/C24H22F3N5O5/c1-23(2,24(25,26)27)19-11-20(32-37-19)31-22(33)30-13-6-5-7-14(8-13)36-21-15-9-17(34-3)18(35-4)10-16(15)28-12-29-21/h5-12H,1-4H3,(H2,30,31,32,33)

HIDE SMILES / InChI

Molecular Formula	C24H22F3N5O5
Molecular Weight	517.4572
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22168626
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24930831 | https://www.ncbi.nlm.nih.gov/pubmed/22319199

CEP-32496 (RXDX 105) is an orally administered, small molecule, VEGFRsparing, RET, BRAF, EGFR tyrosine kinase inhibitor, for the treatment of solid tumours, including malignant melanoma and colorectal cancer. CEP-32496 was originally discovered by Ambit Biosciences (now Daiichi Sankyo) and Cephalon (now owned by Teva) as part of a research programme to develop orally administered kinase inhibitors. The worldwide rights to the compound were licensed to Teva by Ambit, following the acquisition of Cephalon by Teva. Teva, in March 2015, entered into an asset purchase agreement with Ignyta, pursuant to which, Ignyta has acquired worldwide rights and assets of four oncology development programmes, including CEP-32496. Following the acquisition of the compound by Ignyta, CEP 32496 has been renamed to RXDX 105. Phase I/Ib development of RXDX 105 for the treatment of advanced solid tumours is underway in the US.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Serine/threonine-protein kinase B-raf 20 Target ID: CHEMBL5145 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22168626	Inhibitor 8297	14.0 nM [Kd]
Vascular endothelial growth factor receptor 2 104 Target ID: CHEMBL279 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22168626	Inhibitor 8297	8.0 nM [Kd]
Tyrosine-protein kinase receptor RET 14 Target ID: CHEMBL2041 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22168626	Inhibitor 8297	2.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT01877811	Primary		Phase I 428	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY110826	https://www.001chemical.com/chem/search?q=DY110826
001 Chemical	DY445455	https://www.001chemical.com/chem/search?q=DY445455
1PlusChem LLC	1P003A9C	https://www.1pchem.com/search?query=1P003A9C
AChemBlock	M15138	http://www.achemblock.com/catalogsearch/result/?q=M15138
AK Scientific	2310AH	https://aksci.com/item_detail.php?cat=2310AH
AK Scientific	3015AH	https://aksci.com/item_detail.php?cat=3015AH
AbovChem LLC	HY-15199	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-15199
Aceschem	ACF023073	https://www.aceschem.com/catalog/search.do?q=ACF023073
Ambeed	A144993	http://www.ambeed.com/search/Search.html?keyword=A144993
Angene	AGN-PC-0WCQXN	http://www.angenechemical.com/productshow/AGN-PC-0WCQXN.html
ApexBio Technology	A1413	https://www.apexbt.com/catalogsearch/result/?q=A1413
AstaTech	42185	http://astatechinc.com/CPSResult.php?CRNO=42185
BLD Pharm	BD305496	http://www.bldpharm.com/search/Search.html?keyword=BD305496
BLD Pharm	BD558628	http://www.bldpharm.com/search/Search.html?keyword=BD558628
Cayman Chemical	18776	http://www.caymanchem.com/app/template/Product.vm/catalog/18776
Chem Scene	CS-1115	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1115
ChemShuttle	100854	https://www.chemshuttle.com/catalogsearch/result/?q=100854
ChemShuttle	140116	https://www.chemshuttle.com/catalogsearch/result/?q=140116
Excenen	EX-A1481	http://www.excenen.com/searchresultlist.php?id=EX-A1481
Excenen	EX-A1552	http://www.excenen.com/searchresultlist.php?id=EX-A1552
KeyOrganics	AS-74934	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-74934
Matrix Scientific	143691	http://www.matrixscientific.com/143691.html
MedChem Express	HY-15200	https://www.medchemexpress.com/search.html?q=HY-15200&ft=&fa=&fp=
MolPort	MolPort-029-701-896	https://www.molport.com/shop/molecule-link/MolPort-029-701-896
Molcore	MC110826	http://www.molcore.com/CatMC110826.html
Molcore	MC445455	http://www.molcore.com/CatMC445455.html
Molnova	M10648	https://www.molnova.com/en/serch-list.html?keywords=M10648
MuseChem	I000678	https://www.musechem.com/product/I000678.html
Ryan Scientific	RG108	https://ryansci.com/products?q=RG108&list_q=&search_type=exact
Selleck Chemicals	S8015	http://www.selleckchem.com/search.html?searchDTO.searchParam=S8015
ShangHai Biochempartner	BCP06954	http://www.biochempartner.com/search_BCP06954
ShangHai Biochempartner	BCP16304	http://www.biochempartner.com/search_BCP16304
Synthonix	15002	https://synthonix.com/catalogsearch/result/?q=15002
TargetMol	T2070	https://www.targetmol.com/search?keyword=T2070
Tetrahedron	TS89436	http://www.thsci.com/search.do?q=TS89436
W&J PharmaChem	50C2128975	http://wjpharmachem.com/new/searcht.php?keyword=50C2128975
eMolecules	252348639	https://orderbb.emolecules.com/search/#?query=252348639
eMolecules	44811463	https://orderbb.emolecules.com/search/#?query=44811463
eMolecules	44811464	https://orderbb.emolecules.com/search/#?query=44811464
eNovation Chemicals	D501921	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501921&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5238115675	https://mcule.com/MCULE-5238115675/
mcule	MCULE-7120212976	https://mcule.com/MCULE-7120212976/

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

CEP-32496 was evaluated for antitumor efficacy and tolerability in several BRAFV600E-driven human carcinoma xenograft mouse models, including both Colo-205 and A375. Athymic nu/nu nude mice (6-8 week old, 20−25 g) were dosed orally for 14 days with either vehicle only (22% 2-hydroxypropyl-beta-cyclodextrin) or with CEP-32496 at 10, 30, or 100 mg/kg twice daily (BID), and each dose of drug was given in a volume of 0.1 mL per 20 g of body weight. All doses were well tolerated, with no mortality or significant body weight loss (<5% relative to vehicle matched controls) observed during treatment or up to 1 week post dosing. Dosing at 10 mg/kg BID had little effect on tumor growth compared to the control group. However, increasing the dose to either 30 or 100 mg/kg BID resulted in significant efficacy.

Route of Administration: Oral

In Vitro Use Guide

CEP-32496 has demonstrated potent and sustained antiproliferative activity in nanomolar range against A375, Colo-679, Colo-205, SK-MEL-28, HT-144, cell lines expressing BRAFV600E. The CEP-32496 were added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:10:36 GMT 2023` Edited by `admin` on `Fri Dec 15 16:10:36 GMT 2023`
Record UNII	78I4VEX88N
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AGERAFENIB

Official Name

English

RXDX-105

Code

English

RXDX 105 [WHO-DD]

Common Name

English

Agerafenib [WHO-DD]

Common Name

English

CEP-32496

Code

English

AB-024

Code

English

1-(3-((6,7-DIMETHOXYQUINAZOLIN-4-YL)OXY)PHENYL)-3-(5-(1,1,1-TRIFLUORO-2-METHYLPROPAN-2-YL)ISOXAZOL-3-YL)UREA

Systematic Name

English

UREA, N-(3-((6,7-DIMETHOXY-4-QUINAZOLINYL)OXY)PHENYL)-N'-(5-(2,2,2-TRIFLUORO-1,1-DIMETHYLETHYL)-3-ISOXAZOLYL)-

Systematic Name

English

AC-013773

Code

English

agerafenib [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C61074