Nintedanib Ethanesulfonate Salt

Modify Date: 2024-01-02 10:13:59

Nintedanib Ethanesulfonate Salt structure	Common Name	Nintedanib Ethanesulfonate Salt
	CAS Number	656247-18-6	Molecular Weight	649.757
	Density	N/A	Boiling Point	N/A
	Molecular Formula	C₃₃H₃₉N₅O₇S	Melting Point	N/A
	MSDS	N/A	Flash Point	N/A

Use of Nintedanib Ethanesulfonate Salt

Nintedanib esylate (BIBF 1120 esylate) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.

Name	nintedanib esylate
Synonym	More Synonyms

Description	Nintedanib esylate (BIBF 1120 esylate) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC50s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.
Related Catalog	Signaling Pathways >> Protein Tyrosine Kinase/RTK >> FGFR Signaling Pathways >> Protein Tyrosine Kinase/RTK >> PDGFR Research Areas >> Cancer
Target	VEGFR1:34 nM (IC50) VEGFR2:13 nM (IC50) VEGFR3:13 nM (IC50) FGFR1:69 nM (IC50) FGFR2:37 nM (IC50) FGFR3:108 nM (IC50) PDGFRα:59 nM (IC50) PDGFRβ:65 nM (IC50)
In Vitro	Nintedanib (BIBF 1120) binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. Nintedanib (BIBF 1120) inhibits proliferation of PDGF-BB stimulated BRPs with EC50 of 79 nM in cell assays. Nintedanib (BIBF 1120) (100 nM) blocks activation of MAPK after stimulation with 5% serum plus PDGF-BB. Nintedanib (BIBF 1120) prevents PDGF-BB stimulated proliferation with an EC50 of 69 nM in cultures of human vascular smooth muscle cells (HUASMC)[1].
In Vivo	Nintedanib (BIBF 1120) (25-100 mg/kg daily p.o.) is highly active in all tumor models, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model. This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth inhibition[1]. Nintedanib (BIBF 1120) is orally available and displays encouraging efficacy in in vivo tumor models while being well tolerated[2].
Animal Admin	Five-week-old to 6-wk-old athymic NMRI-nu/nu female mice (21-31 g) are used for the assay. After acclimatization, mice are inoculated with 1 to 5×106 (in 100 μL) FaDu, Caki-1, SKOV-3, H460, HT-29, or PAC-120 cells s.c. into the right flank of the animal. After acclimatization, F344 Fischer rats are injected with 5×106 (in 100 μL) GS-9L cells s.c. into the right flank of the animal. For pharmacokinetic analysis, blood is isolated at indicated time points from the retroorbital plexus of mice and plasma is analyzed using high performance liquid chromatography-mass spectrometry methodology[1].
References	[1]. Hilberg F, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res, 2008, 68(12), 4774-4782. [2]. Roth GJ, et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). J Med Chem, 2009, 52(14), 4466-4480. [3]. Suzuki N, et al. Effect of a novel oral chemotherapeutic agent containing a combination of trifluridine, tipiracil and the novel triple angiokinase inhibitor nintedanib, on human colorectal cancer xenografts. Oncol Rep. 2016 Dec;36(6):3123-3130.

Molecular Formula	C₃₃H₃₉N₅O₇S
Molecular Weight	649.757
Exact Mass	649.257019
PSA	160.46000
LogP	4.62470
Storage condition	-20℃

Nintedanib (BIB...

CAS#:656247-17-5

Ethanesulfonic acid

CAS#:594-45-6

~96%

Nintedanib Etha...

CAS#:656247-18-6

Literature: BOEHRINGER INGELHEIM INTERNATIONAL GMBH Patent: WO2009/71523 A1, 2009 ; Location in patent: Page/Page column 4; 25-27 ;

Precursor 2
CAS#:656247-17-5 Nintedanib (BIB... CAS#:594-45-6 Ethanesulfonic acid
DownStream 0

3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate salt

3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-ethylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate

UNII:42F62RTZ4G

methyl (3S,5R)-3,5-di[(tert-butyldimethylsilyl)oxy]-1-hydroxy-cyclohexanecarboxylate

nintedanib ethanesulfonate salt

Ethanesulfonic acid - methyl (3Z)-3-{[(4-{methyl[(4-methyl-1-pipe razinyl)acetyl]amino}phenyl)amino](phenyl)methylene}-2-oxo-6-indo linecarboxylate (1:1)

Nintedanib ethanesulfonate

(3S,5S)-3,5-Bis[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-hydroxy-cyclohexanecarboxylic Acid Methyl Ester

1H-Indole-6-carboxylic acid, 2,3-dihydro-3-[[[4-[methyl[2-(4-methyl-1-piperazinyl)acetyl]amino]phenyl]amino]phenylmethylene]-2-oxo-, methyl ester, (3Z)-, compd. with ethanesulfonic acid (1:1)

methyl (3S,5S)-3,5-bis[tert-butyl(dimethyl)silyloxy]-1-hydroxy-cyclohexanecarboxylate

3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulfonate

Ethanesulfonic acid - methyl (3Z)-3-{[(4-{methyl[(4-methyl-1-piperazinyl)acetyl]amino}phenyl)amino](phenyl)methylene}-2-oxo-6-indolinecarboxylate (1:1)

Vargatef

3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone monoethanesulphonate

Methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate

methyl (3Z)-3-[({4-[N-methyl-2-(4-methylpiperazin-1-yl)acetamido]phenyl}amino)(phenyl)methylidene]-2-oxo-2,3-dihydro-1H-indole-6-carboxylate ethanesulfonate salt

BIBF 1120 esylate

BIBF 1120 (esylate)