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862507-23-1 molecular structure
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5-[2-tert-butyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-3-(2,2-dimethylpropyl)-3H-imidazo[4,5-b]pyridin-2-amine; bis(methanesulfonic acid)

ChemBase ID: 72712
Molecular Formular: C26H37FN6O6S2
Molecular Mass: 612.7369832
Monoisotopic Mass: 612.22000315
SMILES and InChIs

SMILES:
CC(c1nc(c([nH]1)c1nc2c(cc1)nc(n2CC(C)(C)C)N)c1ccc(cc1)F)(C)C.CS(=O)(=O)O.CS(=O)(=O)O
Canonical SMILES:
CS(=O)(=O)O.CS(=O)(=O)O.Fc1ccc(cc1)c1nc([nH]c1c1ccc2c(n1)n(CC(C)(C)C)c(n2)N)C(C)(C)C
InChI:
InChI=1S/C24H29FN6.2CH4O3S/c1-23(2,3)13-31-20-17(28-22(31)26)12-11-16(27-20)19-18(14-7-9-15(25)10-8-14)29-21(30-19)24(4,5)6;2*1-5(2,3)4/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30);2*1H3,(H,2,3,4)
InChIKey:
NARMJPIBAXVUIE-UHFFFAOYSA-N

Cite this record

CBID:72712 http://www.chembase.cn/molecule-72712.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
5-[2-tert-butyl-4-(4-fluorophenyl)-1H-imidazol-5-yl]-3-(2,2-dimethylpropyl)-3H-imidazo[4,5-b]pyridin-2-amine; bis(methanesulfonic acid)
IUPAC Traditional name
5-[2-tert-butyl-5-(4-fluorophenyl)-3H-imidazol-4-yl]-3-(2,2-dimethylpropyl)imidazo[4,5-b]pyridin-2-amine dimesylate
Synonyms
LY2228820
CAS Number
862507-23-1
PubChem SID
162037633
PubChem CID
11570805

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S1494 external link Add to cart Please log in.
Data Source Data ID
PubChem 11570805 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 11.914024  H Acceptors
H Donor LogD (pH = 5.5) 4.944924 
LogD (pH = 7.4) 5.975939  Log P 6.0435834 
Molar Refractivity 120.6971 cm3 Polarizability 49.03102 Å3
Polar Surface Area 85.41 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
p38 MAPK expand Show data source
Salt Data
Mesylate expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S1494 external link
Research Area
Description Cancer
Biological Activity
Description LY2228820 is a novel and potent inhibitor of p38 MAPK with IC50 of 7 nM.
Targets p38α
IC50 7 nM [1]
In Vitro LY2228820 inhibits p38α, as well as the level of phosphoMAPKAPK-2 (pMK2) in RAW 264.7 cells, with IC50 values of 7 nM and 34.3 nM, respectively. Furthermore, LY2228820 inhibits lipopolysaccharide (LPS)-induced TNFα formation in murine peritoneal macrophages, with IC50 of 5.2 nM. [1]In multiple myeloma (MM) cells, including INA6, RPMI-8226, U266, and RPMI-Dox40, LY2228820 (200 nM–800 nM) significantly blocks p38MAPK signaling, as revealed by its inhibition on phosphorylation of HSP27, a downstream target of p38MAPK, without affecting the expression level of HSP27. LY2228820 (200 nM–400 nM) enhances bortezomib-induced cytotoxicity and apoptosis, but LY2228820 alone doesn’t inhibit the growth of MM.1S cells. LY2228820 (200 nM–800 nM) also inhibits secretion of IL-6 and MIP-1α in long-term BM stromal cells (LT-BMSCs), BM mononuclear cells (BMMNCs), peripheral blood (PB) CD138+, CD138? or PB CD14+ cells. LY2228820 (400 nM–800 nM) also blocks osteoclastogenesis from CD14+ cells. [2]
In Vivo In LPS-induced mice, LY2228820 effectively inhibits the formation of TNFα with a threshold minimum 50% effective dose (TMED50) less than 1 mg/kg. In a rat model of collagen-inducedarthritis (CIA), LY2228820 displays potent effects on paw swelling, bone erosion, and cartilage destruction, with a threshold minimum 50% effective dose (TMED50)of 1.5 mg/kg. [1]
Clinical Trials LY2228820 is currently under a Phase I clinical trial for the treatment of advanced cancer.
Features
Protocol
Kinase Assay [1]
Inhibition of p38α Inhibition of p38α is determined using recombinant human p38α in a standard filter binding protocol using ATP[γ-33P] and EGFR 21-mer peptide as substrate. Functional inhibition of TNFα in murine peritoneal macrophages is determined using LPS stimulation in the presence of LY2228820. To assess p38α activity in cells more directly, RAW 264.7 cells are treated with LY2228820 and then stimulated with anisomycin. The level of p38α activity is detected using a phosphoMAPKAPK-2 (pMK2) (Thr 334) antibody which reacts with a residue specifically phosphorylated by p38α.
Cell Assay []
Cell Lines MM cells, including INA6, RPMI-8226, U266, and RPMI-Dox40
Concentrations 200 nM–800 nM
Incubation Time 48 hours
Methods MTT assays and APO 2.7 staining are performed to assess cellular proliferation and induction of apoptosis, respectively. Viability is expressed as percent viable cells. Apoptosis in cells is evaluated by APO 2.7 staining. For detection of mitochondrial membrane protein 7A6 expressed in apoptotic cells, cells are incubated with APO 2.7 reagent for 20 min. Expression of APO 2.7 is determined using an EPICS XL flow cytometer.
Animal Study [1]
Animal Models Lipopolysaccharide (LPS)-induced Balb/c mice
Formulation Dissolved in 1% CMC/0.25% Tween 80 in water
Doses 0–20 mg/kg
Administration Oral bid dosing for 14 days
References
[1] Mader M, et al. Bioorg Med Chem Lett, 2008, 18(1), 179-183.
[2] Ishitsuka K, et al. Br J Haematol, 2008, 141(5), 598-606.
[3] Ishitsuka K, et al. Oncogene, 2005, 24(38), 5888-5896.

REFERENCES

REFERENCES

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