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859212-16-1 molecular structure
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4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-N-(4-methyl-3-{[5-(pyrimidin-5-yl)pyrimidin-2-yl]amino}phenyl)-3-(trifluoromethyl)benzamide

ChemBase ID: 72642
Molecular Formular: C30H31F3N8O
Molecular Mass: 576.6153496
Monoisotopic Mass: 576.25729231
SMILES and InChIs

SMILES:
n1cncc(c1)c1cnc(nc1)Nc1cc(ccc1C)NC(=O)c1ccc(c(c1)C(F)(F)F)CN1CC[C@@H](C1)N(C)C
Canonical SMILES:
CN([C@H]1CCN(C1)Cc1ccc(cc1C(F)(F)F)C(=O)Nc1ccc(c(c1)Nc1ncc(cn1)c1cncnc1)C)C
InChI:
InChI=1S/C30H31F3N8O/c1-19-4-7-24(11-27(19)39-29-36-14-23(15-37-29)22-12-34-18-35-13-22)38-28(42)20-5-6-21(26(10-20)30(31,32)33)16-41-9-8-25(17-41)40(2)3/h4-7,10-15,18,25H,8-9,16-17H2,1-3H3,(H,38,42)(H,36,37,39)/t25-/m0/s1
InChIKey:
ZOPBZHLJXQAQON-VWLOTQADSA-N

Cite this record

CBID:72642 http://www.chembase.cn/molecule-72642.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-N-(4-methyl-3-{[5-(pyrimidin-5-yl)pyrimidin-2-yl]amino}phenyl)-3-(trifluoromethyl)benzamide
IUPAC Traditional name
4-{[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl}-N-(4-methyl-3-{[5-(pyrimidin-5-yl)pyrimidin-2-yl]amino}phenyl)-3-(trifluoromethyl)benzamide
Synonyms
INNO-406
NS-187
Bafetinib
CAS Number
859212-16-1
PubChem SID
162037567
PubChem CID
24853523

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S1369 external link Add to cart Please log in.
Data Source Data ID
PubChem 24853523 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 12.333137  H Acceptors
H Donor LogD (pH = 5.5) 0.8895569 
LogD (pH = 7.4) 2.2248895  Log P 4.2835603 
Molar Refractivity 158.6318 cm3 Polarizability 58.948284 Å3
Polar Surface Area 99.17 Å2 Rotatable Bonds
Lipinski's Rule of Five false 

PROPERTIES

PROPERTIES

Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Target
Bcr-Abl expand Show data source
Salt Data
Free Base expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S1369 external link
Research Area
Description Chronic myeloid leukaemia
Biological Activity
Description Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM and 19 nM, respectively.
Targets Abl Lyn
IC50 5.8 nM 19 nM [1]
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]
Clinical Trials Bafetinib is currently in Phase II clinical trials in patients with hormone refractory prostate cancer.
Features Dual Bcr-Abl/Lyn inhibitor
Protocol
Kinase Assay [1]
Kinase assay Bcr-Abl kinase assays are performed in 25 μL of reaction mixture containing 250 μM peptide substrate, 740 Bq/μL [γ-33P]ATP, and 20 μM 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.
Cell Assay [1]
Cell Lines K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells
Concentrations 0-10 μM
Incubation Time 72 hours
Methods 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.
Animal Study [1]
Animal Models KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice.
Formulation Bafetinib is dissolved in 0.5% methylcellulose.
Doses ≤20 mg/kg/day
Administration Administered via p.o.
References
[1] Kimura S, et al. Blood. 2005, 106(12), 3948-3954.
[2] Kamitsuji Y, et al. Cell Death Differ. 2008, 15(11), 1712-2172.
[3] Yokota A, et al. Blood. 2007, 109(1), 306-314.

REFERENCES

REFERENCES

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