TAK-779, inhibitor

TAK-779

Cat. Num. AAA5758394

• Purity: 98.00%
• Synonyms: TAK-779; Takeda 779; inhibitor

• Purity/Purification: 98.00%
• Form/Format: Solid. Powder

• Solubility: DMSO: 25mg/mL (47.07mM); Ethanol: 62mg/mL (186.5mM); Water: <1mg/mL; H2O: 16.66mg/mL (31.37mM); (<1mg/ml refers to the product slightly soluble or insoluble)
• Formula: C33H39ClN2O2
• SMILES: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(C[N+](C)(C)C4CCOCC4)cc2)CCC3)cc1.[Cl-]
• CAS Number: 229005-80-5
• Target & IC50: Abl: ic50 14nM; Abl (T315I): ic50 4nM; Aurora A: ic50 48nM; FGFR1: ic50 36nM; FLT3: ic50 6.6nM; FLT3 (D835Y): ic50 1nM; JAK2: ic50 150nM; Kit: ic50 300nM; Src: ic50 400nM; MIP-1alpha-CCR5: ic50 1nM (in CHO/CCR5 cells); MIP-1beta-CCR5: ic50 1nM (in CHO/CCR5 cells); RANTES-CCR5: ic50 1.4nM (in CHO/CCR5 cells); MCP-1-CCR2b: ic50 27nM (in CHO/CCR5 cells); R5 HIV-1 (Ba-L): ic50 3.7nM (EC50, in PBMCs); R5 HIV-1 (KK): ic50 1.6nM (EC50, in PBMCs); CCR2; CXCR
• Cell Research: Cell viability is determined by the sodium 3'-[1-(phenylaminocarbonyl)-3, 4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate assay after incubation with or without KW-2449 for 72 hours at 37 degree C. The number of viable cells is determined using the Cell Proliferation Kit II. For cell-cycle analysis, MOLM-13 and RS4;11 cells are treated with KW-2449. After 24, 48, and 72 hours of incubation at 37 degree C, DNA contents are analyzed. Cell cycle distribution of K562, TCC-Y, and TCC/Ysr is analyzed 24 hours after treatment with KW-2449 or imatinib. (Only for Reference) Cell lines: MOLM-13 and RS4;11 cells
• Kinase Assay: FLT3 phosphorylation: Leukemia cells are washed in phosphate-buffered saline (PBS), then lysed by resuspending the cells in lysis buffer (20mM Tris pH 7.4, 100mM NaCl, 1% Igepal, 1mM EDTA, 2mM NaVO4, plus Complete protease inhibitor KW-2449 for 30 minutes while rocking. The extract is clarified by centrifugation at 1.6 × 104g and the supernatant is assayed for protein (Bio-Rad). A 50-ug aliquot is removed as a whole-cell lysate for analysis of STAT5, and the remainder is used for immunoprecipitation with anti-FLT3. Anti-FLT3 antibody is added to the extract for overnight incubation, then protein A sepharose is added for 2 additional hours. Separate sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) gels for whole-cell lysate and immunoprecipates are run in parallel. After transfer to Immobilon membranes, immunoblotting is performed with antiphosphotyrosine antibody (4G10) to detect phosphorylated FLT3 or, for the whole-cell lysate gels, with a rat monoclonal antibody against phosphorylated STAT5 (residue Y694) then stripped and reprobed with anti-FLT3 antibody to measure total FLT3. Proteins are visualized using chemiluminescence, exposed on Kodak BioMax XAR film, developed, and scanned using a Bio-Rad GS800 densitometer. The concentration of KW-2449 for which the phosphorylation of FLT3 or STAT5 is inhibited to 50% of its baseline (IC50) is determined using linear regression analysis of the dose response curves. For direct analysis of FLT3 and STAT5 in circulating blasts, peripheral blood is collected in heparinized tubes and promptly chilled on ice. Samples are centrifuged for 10 minutes at 900 g, at 4 degree C. The plasma is removed and stored frozen at -80 degree C. The buffy coat is carefully transferred to ice-cold PBS, layered onto chilled Ficoll-Hypaque, and centrifuged for 5 minutes at 600 g, at 4 degree C. All subsequent steps are carried out at 4 degree C. Mononuclear cells are collected and washed rapidly once in red blood cell lysis buffer (0.155M NH4Cl, 0.01 M KHCO3, 0.1mM EDTA), then washed once in PBS. Cells are then lysed as described for FLT3 and STAT5 analysis.
• In Vitro: TAK-779 increases intestinal allograft survival in a rat model of small intestine transplantation when administered at a dose of 10mg/kg per day[2].
• Preparation and Storage: Store at -20 degree C for 3 years powder; -80 degree C for 2 years in solvent

Structure

Related Product Information for TAK-779, inhibitor

TAK-779 is an antagonist of chemokine receptor 5 (CCR5), CCR2b, and CXC chemokine receptor 3 (CXCR3).

Product Categories/Family for TAK-779, inhibitor

Angiogenesis; FGFR; Microbiology&virology; Immunology/Inflammation; Autophagy; GPCR/G Protein

References

Shiotsu Y, et al. Blood, 2009, 114(8), 1607-17.
Suzaki Y, Hamada K, Nomi T, et al. A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation[J]. European Respiratory Journal, 2008, 31(4):783-789.
Suzaki Y, Hamada K, Nomi T, et al. A small-molecule compound targeting CCR5 and CXCR3 prevents airway hyperresponsiveness and inflammation[J]. European Respiratory Journal, 2008, 31(4):783-789.
Pratz KW, et al. Blood, 2009, 113(17), 3938-46.
Takama Y, Miyagawa S, Yamamoto A, et al. Effects of a calcineurin inhibitor, FK506, and a CCR5/CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model[J]. Transplant Immunology, 2011, 25(1):0-55.
Takama Y, Miyagawa S, Yamamoto A, et al. Effects of a calcineurin inhibitor, FK506, and a CCR5/CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model[J]. Transplant Immunology, 2011, 25(1):0-55.
Nguyen T, et al. Clin Cancer Res, 2011, 17(10), 3219-32.