Vergleich

Bafetinib Europäischer Partner

ArtNr S1369-200
Hersteller Selleckchem
CAS-Nr. 859212-16-1
Menge 200 mg
Quantity options 10 mg 100 mg 10 mM/1 mL 1 g 200 mg 25 mg 5 mg 50 mg
Kategorie
Typ Inhibitors
Specific against other
Smiles CC1=C(C=C(C=C1)NC(=O)C2=CC(=C(C=C2)CN3CCC(C3)N(C)C)C(F)(F)F)NC4=NC=CC(=N4)C5=CN=CN=C5
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias INNO-406,NS-187
Similar products Bafetinib
Lieferbar
Manufacturer - Targets
LYN, BCR
Storage Conditions
2 years -80 in solvent
Molecular Weight
576, 62
Administration
Administered via p.o.
Animal Models
KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice.
Cell lines
K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells
Clinical Trials
Bafetinib is currently in Phase II clinical trials in patients with hormone refractory prostate cancer.
Concentrations
0-10 uM
Dosages
<=20 mg/kg/day
Formulation
Bafetinib is dissolved in 0.5% methylcellulose.
IC50
5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM
In vitro
Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells, respectively. Bafetinib suppresses the growth of the Bcr-Abl-positive cell lines including K562, KU812, and BaF3/wt cells potently without effects on the proliferation of the Bcr-Abl-negative U937 cell line. Moreover, Bafetinib exhibits a dose-dependent antiproliferative effect against Bcr-Abl point mutant cell lines, such as BaF3/E255K cells. [1] In Bcr-Abl+ leukemia cell lines, Bafetinib induces both caspase-mediated and caspase-independent cell death by blocking the phosphorylation of Bcr-Abl. [2]
In vivo
In Bcr-Abl–positive KU812 mouse model, Bafetinib (0.2 mg/kg/day) significantly inhibits tumor growth, and completely inhibits tumor growth without adverse effects at 20 mg/kg/day. For Balb/c mice, Bafetinib shows maximal tolerated dose of 200 mg/kg/d and bioavailability value (BA) of 32%. [1] In a Central nervous system (CNS) leukemia model bearing Ba/F3/wt bcr-ablGFP, Ba/F3/Q252H, or Ba/F3/M351T cells, combination treatment of Bafetinib (60 mg/kg) and cyclosporine A (CsA) (50 mg/kg) leads to more significant inhibition of leukemia growth in the brain than either Bafetinib or CsA alone. [3]
Incubation Time
72 hours
Kinase Assay
Kinase assay, Bcr-Abl kinase assays are performed in 25 uL of reaction mixture containing 250 uM peptide substrate, 740 Bq/uL [gamma-33P]ATP, and 20 uM cold adenosine triphosphate (ATP) by using the SignaTECT protein tyrosine kinase assay system. Each Bcr-Abl kinase is used at a concentration of 10 nM. Kinase assays for Abl, Src, and Lyn are carried out with an enzyme-linked immunosorbent assay (ELISA) kit. The inhibitory effects of NS-187 against 79 tyrosine kinases are tested with KinaseProfiler.
Method
K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells are plated at 1, 103 in 96-well plates, whereas KU812 and U937 cells are plated at 5, 103 in 96-well plates. Cells are incubated with serial dilutions of Bafetinib for 3 days. Cell proliferation is measured by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, Nacalai Tesque) assay, and the 50% inhibitory concentration (IC50) values are calculated by fitting the data to a logistic curve.
Information
Bafetinib is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM in cell-free assays, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit.
Chemical Name
(S)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-N-(4-methyl-3-(4-(pyrimidin-5-yl)pyrimidin-2-ylamino)phenyl)-3-(trifluoromethyl)benzamide
Features
Dual Bcr-Abl/Lyn inhibitor

Hinweis: Die dargestellten Informationen und Dokumente (Bedienungsanleitung, Produktdatenblatt, Sicherheitsdatenblatt und Analysezertifikat) entsprechen unserem letzten Update und sollten lediglich der Orientierung dienen. Wir übernehmen keine Garantie für die Aktualität. Für spezifische Anforderungen bitten wir Sie, uns eine Anfrage zu stellen.

Alle Produkte sind nur für Forschungszwecke bestimmt. Nicht für den menschlichen, tierärztlichen oder therapeutischen Gebrauch.

Menge: 200 mg
Lieferbar: In stock
lieferbar

Vergleichen

Auf den Wunschzettel

Angebot anfordern

Lieferzeit anfragen

Technische Frage stellen

Bulk-Anfrage stellen

Fragen zum Produkt?