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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C17H14BrN3O |
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分子量 | 356.22 | CAS No. | 857064-38-1 | ||||||||
Solubility (25°C)* | 体外 | DMSO | 71 mg/mL (199.31 mM) | ||||||||
Water | Insoluble | ||||||||||
Ethanol | Insoluble | ||||||||||
体内 (毎回新しく調製した物を用意してください) |
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | WP1066 is a novel inhibitor of JAK2 and STAT3 with IC50 of 2.30 μM and 2.43 μM in HEL cells; shows activity to JAK2, STAT3, STAT5, and ERK1/2 not JAK1 and JAK3. WP1066 induces apoptosis. Phase 1. |
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in vitro | WP1066 markedly inhibits the growth of HEL cells carrying the JAK2 V617F mutant isoform in a dose-dependent manner with IC20, IC50 and IC80 of 0.8, 2.3 and 3.8 μM. WP1066 at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM inhibits the phosphorylation of JAK2, STAT3, STAT5, and ERK1/2 without affecting the phosphorylation of JAK1 and JAK3 in erythroid leukemia HEL cells that express the JAK2 V617F isoform. [1] WP1066 at concentrations ranging from 0.5 to 3.0 μM inhibits the proliferation of AML colony-forming cells obtained from patients and that of the AML cell lines OCIM2 and K562 in a dose-dependent manner. WP1066 at concentrations of 0.5, 1.0, 2.0, 3.0, or 4.0 μM dose-dependently decreases JAK2 and pJAK2 protein levels as well as downstream phosphorylation levels of STAT3, STAT5, and AKT in OCIM2 and K562 cells. WP1066 at concentrations of 2 μM inhibits OCIM2 cell multiplication by inducing accumulation of cells at the G0-G1 phase of the cell cycle. WP1066 at concentrations of 1, 2, or 3 μM induces apoptosis in both OCIM2 and K562 cells in a dose-dependent fashion by activating procaspase-3 and cleaving PARP. [3] WP1066 at concentrations of 5 μM prevents the phosphorylation of STAT3, and at concentrations of 2.5μM WP1066 significantly inhibits cell survival and proliferation in Caki-1 and 786-O renal cancer cells. WP1066 at concentrations of 5 μM suppresses HIF1α and HIF2α expression and VEGF production in Caki-1 and 786-O renal cancer cells. [4] |
in vivo | WP1066 orally administrated at dose of 40 mg/kg once daily for 19 days significantly inhibits the tumours growth in Caki-1 xenograft mice, with decreased immunostaining of phosphorylated STAT3 and reduced length of CD34-positive vessels. [4] |
特徴 | Similar to its parent compound AG490, WP1066 inhibits the phosphorylation of JAK2, but unlike AG490, WP1066 also degraded JAK2 protein. |
細胞アッセイ | 細胞株 | HEL cells carrying the JAK2 V617F mutant isoform, HL60, K562, Raji, PEER, CMK, TM and RHN cells |
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濃度 | 0 - 6 μM | |
反応時間 | 72 hours | |
実験の流れ | The 3, [4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTT) assay is done using an MTT-based cell proliferation/cytotoxicity assay system. Briefly, fresh low-density peripheral blood cells and various cell lines at the logarithmic phase of their growth are washed twice in RPMI 1640 containing 10% FCS and counted in a hemocytometer. Cell viability is assessed by the trypan blue (0.1%) staining method. Equal numbers of viable cells (5 × 104 per well) are incubated in a total volume of 100 μL of RPMI 1640 supplemented with 10% FCS alone or with WP1066 at increasing concentrations; the incubations are continued for up to 72 h in 96-well flat-bottomed plates at 37 °C in a humidified 5% CO2 atmosphere. Experiments for each condition are done in triplicate. After incubation, 20 μL of CellTiter96 One Solution Reagent are added to each well. The plates are then incubated for an additional 60 min at 37 °C in a humidified 5% CO2 atmosphere. Immediately after incubation, absorbance is read using a 96-well plate reader at a wavelength of 490 nm. | |
動物実験 | 動物モデル | Caki-1 xenograft mice |
投薬量 | 40 mg/kg | |
投与方法 | Orally administrated |
Data from [Data independently produced by J Biol Chem, 2013, 288(36), 26167-76]
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Data from [Data independently produced by , , Clin Cancer Res, 2018, 24(11):2665-2677]
Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression [ Nat Commun, 2024, 15(1):1987] | PubMed: 38443336 |
IGFBP3 induces PD-L1 expression to promote glioblastoma immune evasion [ Cancer Cell Int, 2024, 24(1):60] | PubMed: 38326861 |
P. gingivalis Infection Upregulates PD-L1 Expression on Dendritic Cells, Suppresses CD8+ T-cell Responses, and Aggravates Oral Cancer [ Cancer Immunol Res, 2023, 11(3):290-305] | PubMed: 36633576 |
P. gingivalis Infection Upregulates PD-L1 Expression on Dendritic Cells, Suppresses CD8+ T-cell Responses, and Aggravates Oral Cancer [ Cancer Immunol Res, 2023, 11(3):290-305] | PubMed: 36633576 |
Tumor-associated astrocytes promote tumor progression of Sonic Hedgehog medulloblastoma by secreting lipocalin-2 [ Brain Pathol, 2023, 10.1111/bpa.13212] | PubMed: 37721122 |
oHSV-P10 reduces glioma stem cell enrichment after oncolytic HSV therapy [ Mol Ther Oncolytics, 2023, 29:30-41] | PubMed: 37114074 |
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ Int Immunopharmacol, 2023, 118:109993] | PubMed: 36931170 |
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ Int Immunopharmacol, 2023, 118:109993] | PubMed: 36931170 |
Triptolide reduces PD-L1 through the EGFR and IFN-γ/IRF1 dual signaling pathways [ International Immunopharmacology, 2023, Volume 118] | PubMed: None |
STAT3 Inhibition Attenuates MYC Expression by Modulating Co-Activator Recruitment and Suppresses Medulloblastoma Tumor Growth by Augmenting Cisplatin Efficacy In Vivo [ Cancers (Basel), 2023, 15(8)2239] | PubMed: 37190167 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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