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405554-55-4 molecular structure
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[2-(4-{5-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-4-(pyridin-4-yl)-1H-imidazol-2-yl}phenoxy)ethyl]dimethylamine

ChemBase ID: 72908
Molecular Formular: C27H27N5O2
Molecular Mass: 453.53558
Monoisotopic Mass: 453.21647513
SMILES and InChIs

SMILES:
n1c(c([nH]c1c1ccc(cc1)OCCN(C)C)c1ccc2c(c1)CC/C/2=N\O)c1ccncc1
Canonical SMILES:
O/N=C/1\CCc2c1ccc(c2)c1[nH]c(nc1c1ccncc1)c1ccc(cc1)OCCN(C)C
InChI:
InChI=1S/C27H27N5O2/c1-32(2)15-16-34-22-7-3-19(4-8-22)27-29-25(18-11-13-28-14-12-18)26(30-27)21-5-9-23-20(17-21)6-10-24(23)31-33/h3-5,7-9,11-14,17,33H,6,10,15-16H2,1-2H3,(H,29,30)/b31-24+
InChIKey:
MLSAQOINCGAULQ-QFMPWRQOSA-N

Cite this record

CBID:72908 http://www.chembase.cn/molecule-72908.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
[2-(4-{5-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-4-(pyridin-4-yl)-1H-imidazol-2-yl}phenoxy)ethyl]dimethylamine
IUPAC Traditional name
[2-(4-{4-[(1E)-1-(hydroxyimino)-2,3-dihydroinden-5-yl]-5-(pyridin-4-yl)-3H-imidazol-2-yl}phenoxy)ethyl]dimethylamine
Synonyms
SB 590885
SB590885
CAS Number
405554-55-4
PubChem SID
162037828
PubChem CID
11316960

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S2220 external link Add to cart Please log in.
Data Source Data ID
PubChem 11316960 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 8.433906  H Acceptors
H Donor LogD (pH = 5.5) 0.84019864 
LogD (pH = 7.4) 2.621574  Log P 3.3556507 
Molar Refractivity 143.7071 cm3 Polarizability 54.187893 Å3
Polar Surface Area 86.63 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

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

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2220 external link
Research Area
Description Cancer
Biological Activity
Description SB590885 is a potent B-Raf inhibitor with Ki of 0.16 nM.
Targets B-Raf
IC50 0.16 nM (Ki) [1]
In Vitro SB590885 displays significant selectivity for B-Raf over c-Raf with Ki of 0.16 nM over 1.72 nM. SB-590885 is a more potent inhibitor than the previously described Raf/VEGFR kinase inhibitor BAY 439006 (Ki = 38 nM for mutant B-Raf, 6 nM for c-Raf). SB590885 displays potent selectivity over 46 other kinases. Unlike the multi-kinase inhibitor BAY43-9006, SB590885 stabilizes the oncogenic B-Raf kinase domain in an active configuration. In Colo205, HT29, A375P, SKMEL28, and MALME-3M cells expressing oncogenic B-RafV600E, SB590885 treatment potently inhibits ERK phosphorylation with EC50 of 28 nM, 58 nM, 290 nM, 58 nM, and 190 nM, respectively, and consistently, inhibits the proliferation with EC50 of 0.1 μM, 0.87 μM, 0.37 μM, 0.12 μM, and 0.15 μM, respectively. SB590885 decreases anchorage-independent growth of melanoma cell lines in a BRAF mutant-selective manner. [1] SB590885 displays high affinity for B-Raf with Kd of 0.3 nM. [2] Most of the melanoma cell lines that harbor the BRAF V600E mutation and lack CDK4 mutations (451Lu, WM35, and WM983) are highly sensitive to SB590885 with IC50 of <1 μm.="" increased="" levels="" of="" cyclin="" d1="" resulting="" from="" genomic="" amplification="" mediate="" sb590885="" resistance="" in="" b-raf="" v600e-mutated="" melanomas.="">[3]
In Vivo Administration of SB590885 potently decreases tumorigenesis in murine xenografts established from mutant B-Raf-expressing A375P melanoma cells, and modestly inhibits tumor growth. [1]
Clinical Trials
Features SB590885 displays significant selectivity for B-Raf over c-Raf.
Protocol
Cell Assay [1]
Cell Lines Colo205, HT29, A375P, SKMEL28, and MALME-3M
Concentrations Dissolved in DMSO, final concentrations ~10 μM
Incubation Time 72 hours
Methods Cells are treated with increasing concentrations of SB590885 and incubated for 72 hours. Viable cells are quantified using CellTiter-Glo reagent and luminescence detection on a Victor 2V plate reader. Cells are prepared for cell cycle analysis on a Becton Dickinson FACScan. Data is acquired and analyzed using CellQuest v3.3 software.
Animal Study [1]
Animal Models Female nude mice injected s.c. with of A375P cells
Formulation Dissolved in vehicle [2% N,N-dimethylacetamide, 2% Cremophor EL, and 96% acidified water (pH f4–5)]
Doses 50 mg/kg/day
Administration Injection i.p.
References
[1] King AJ, et al. Cancer Res, 2006, 66(23), 11100-11105.
[2] Takle AK, et al. Bioorg Med Chem Lett, 2006, 16(2), 378-381.
[3] Smalley KS, et al. Mol Cancer Ther, 2008, 7(9), 2876-2883.

REFERENCES

REFERENCES

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PATENTS

PATENTS

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