AZD1480 is a potent JAK2 inhibitor with an IC50 of 0.26 nM. AZD1480 inhibits constitutive and stimulus-induced phosphorylation of JAK2 and STAT-3 in vitro, downstream gene expression, and inhibits cell proliferation. AZD1480 suppresses STAT-3 activation in the glioma-initiating cell population in glioblastoma (GBM) tumors. In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial GBM tumors by inhibiting STAT-3 activity. Importantly, AZD1480 induces cell death of Kms.11 cells grown in the presence of HS-5 bone marrow (BM)-derived stromal cells and inhibits tumor growth in a Kms.11 xenograft mouse model, accompanied with inhibition of phospho-FGFR3, phospho-JAK2, phospho-STAT3 and Cyclin D2 levels. AZD1480 blocks proliferation, survival, FGFR3 and JAK/STAT3 signaling in myeloma cells cultured alone or cocultured with BM stromal cells, and in vivo, and leads to a decrease in cell proliferation and induction of apoptosis.
|Cell lines||Renca or 786-O cells|
|Preparation method||Cell viability assay.
Renca or 786-O cells suspended in DMEM medium with 5% FBS were seeded in 96-well plates (5,000 per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 h. Cell viability was determined by MTS assay (Promega, Madison, WI) according to instructions. Absorbance at 490 nm was measured with Mikrotek Laborsysteme (Overath, Germany). Mouse ECs and splenic CD11b+/c− myeloid cells enriched from tumor bearing mice were cultured in 5% FBS 1640 RPMI medium. HUVECs were cultured on collagen 1-coated plates in complete medium (Clonetics). All cells are treated with DMSO and AZD1480 at various doses for 24 h. Cell viability was determined by counting cell number manually. All the experiments were repeated 3 times.
|Concentrations||0, 0.1, 0.5, 1.0, 2.5, and 5 μM|
|Incubation time||48 h|
|Animal models||Female BALB/c and athymic nude (NCR-nu/nu) mice (7-8 weeks old)|
|Formulation||water supplemented with 0.5% Hypromellose and 0.1% Tween 80|
|Dosages||50 mg/kg once a day or 30 mg/kg twice daily for 21 days|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 65 mg/mL|
The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma.
Derenzini E, et al. Blood Cancer J. 2011 Dec;1(12):e46. PMID: 22829094.
Therapeutic potential of AZD1480 for the treatment of human glioblastoma.
McFarland BC, et al. Mol Cancer Ther. 2011 Dec;10(12):2384-93. PMID: 22027691.
Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480.
Xin H, et al. Cancer Res. 2011 Nov 1;71(21):6601-10. PMID: 21920898.
The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival.
Scuto A, et al. Leukemia. 2011 Mar;25(3):538-50. PMID: 21164517.
The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors.
Hedvat M, et al. Cancer Cell. 2009 Dec 8;16(6):487-97. PMID: 19962667.
|Related JAK Products|
Delphinidin (chloride) is an anthocyanidin, a natural plant pigment which can modulate JAK/STAT3 and MAPKinase signaling to induce apoptosis in HCT116 cells.
AZD4205 is a novel potent and selective janus kinase 1 (JAK1) inhibitor, with IC50 value of 73 nM.
PF-06826647, also known as Tyk2-IN-8, is a selective and orally administered tyrosine kinase 2 (TYK2) inhibitor, with IC50 of 17 nM.
PF-06700841 (Brepocitinib) tosylate is a dual inhibitor of JAK1 and TYK2, with IC50 values of 17 nM and 23 nM, respectively.
|JAK3-IN-6 (Compound 2)
JAK3-IN-6 (Compound 2) CAS#: 1443235-95-7 is a potent and highly selective JAK3 inhibitor, with an IC50 of 0.15 nM.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.