Ralimetinib dimysylate(LY2228820 dimysylate)

Molecular Weight (MW)	612.74
Formula	C24H29FN6.2CH4O3S
CAS No.	862507-23-1
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 4 mg/mL warmed (6.5 mM)
Water: 100 mg/mL (163.2 mM)
Ethanol: 3 mg/mL (4.9 mM)
Solubility (In vivo)	Saline: 30 mg/mL
Synonyms	LY-2228820; LY 2228820; Ralimetinib; LY2228820;LY2228820 dimesylate; Ralimetinib dimesylate Chemical Name: 5-(2-(tert-butyl)-5-(4-fluorophenyl)-1H-imidazol-4-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine InChi Key: XPPBBJCBDOEXDN-UHFFFAOYSA-N InChi Code: InChI=1S/C24H29FN6/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/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30) SMILES Code: NC1=NC2=CC=C(C3=C(C4=CC=C(F)C=C4)NC(C(C)(C)C)=N3)N=C2N1CC(C)(C)C

Molecular Weight (MW)

612.74

Formula

C24H29FN6.2CH4O3S

CAS No.

862507-23-1

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 4 mg/mL warmed (6.5 mM)

Water: 100 mg/mL (163.2 mM)

Ethanol: 3 mg/mL (4.9 mM)

Solubility (In vivo)

Saline: 30 mg/mL

Synonyms

LY-2228820; LY 2228820; Ralimetinib; LY2228820;LY2228820 dimesylate; Ralimetinib dimesylate

Chemical Name: 5-(2-(tert-butyl)-5-(4-fluorophenyl)-1H-imidazol-4-yl)-3-neopentyl-3H-imidazo[4,5-b]pyridin-2-amine

InChi Key: XPPBBJCBDOEXDN-UHFFFAOYSA-N

InChi Code: InChI=1S/C24H29FN6/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/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30)

SMILES Code: NC1=NC2=CC=C(C3=C(C4=CC=C(F)C=C4)NC(C(C)(C)C)=N3)N=C2N1CC(C)(C)C

In Vitro	In vitro activity: 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. 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. Kinase Assay: 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: 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.
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.
Animal model	Lipopolysaccharide (LPS)-induced Balb/c mice
Formulation & Dosage	Dissolved in 1% CMC/0.25% Tween 80 in water; 0–20 mg/kg; Administered via p.o.
References	Bioorg Med Chem Lett. 2008 Jan 1;18(1):179-83; Br J Haematol. 2008 May;141(5):598-606.

In Vitro

In vitro activity: 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. 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.

Kinase Assay: 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: 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.

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.

Animal model

Lipopolysaccharide (LPS)-induced Balb/c mice

Formulation & Dosage

Dissolved in 1% CMC/0.25% Tween 80 in water; 0–20 mg/kg; Administered via p.o.

References

Bioorg Med Chem Lett. 2008 Jan 1;18(1):179-83; Br J Haematol. 2008 May;141(5):598-606.

CAS NO:	862507-23-1
规格:	≥98%

包装	价格(元)
5mg	电议
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议