Home JAK/STAT JAK inhibitor AZD1480 For research use only.

AZD1480

AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.

AZD1480 Chemical Structure

AZD1480 Chemical Structure

CAS No. 935666-88-9

Purity & Quality Control

AZD1480 Related Products

Signaling Pathway

JAK Signaling Pathways

JAK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
SW620 Function Assay 5 μM 48 h DMSO blocks JAK2/STAT3 signaling 25954974
LoVo  Function Assay 5 μM 48 h DMSO blocks JAK2/STAT3 signaling 25954974
HN5 Growth Inhibition Assay 72 h EC50=3.81 ± 1.99 μM 25810010
Cal33 Growth Inhibition Assay 72 h EC50=3.37 ± 0.75 μM 25810010
UM-22B Growth Inhibition Assay 72 h EC50=2.66 ± 0.24 μM 25810010
686LN Growth Inhibition Assay 72 h EC50=2.05 ± 1.33 μM 25810010
UM SCC-1 Growth Inhibition Assay 72 h EC50=1.67 ± 0.42 μM 25810010
UM-22A Growth Inhibition Assay 72 h EC50=1.32 ± 0.39 μM 25810010
OSC19 Growth Inhibition Assay 72 h EC50=1.26 ± 0.20 μM 25810010
PCI-52 Growth Inhibition Assay 72 h EC50=1.00 ± 0.09 μM 25810010
PCI-15B Growth Inhibition Assay 72 h EC50=0.99 ± 1.74 μM 25810010
UMSCC-1 Function Assay 0.0005-1.6 μM 24 h abrogates IL-6–induced up-regulation of pSTAT3Tyr705 in a dose-dependent manner 25810010
Cal33 Function Assay 0.0005-3.8 μM 24 h abrogates IL-6–induced up-regulation of pSTAT3Tyr705 in a dose-dependent manner 25810010
HH5 Function Assay 0.0005-3.8 μM 24 h abrogates IL-6–induced up-regulation of pSTAT3Tyr705 in a dose-dependent manner 25810010
UM-22A Function Assay 0.0005-1.6 μM 24 h abrogates IL-6–induced up-regulation of pSTAT3Tyr705 in a dose-dependent manner 25810010
A1847 Function Assay 0.05-10 μM 24 h DMSO  reduces phosphorylated STAT3 levels 25646015
OVCAR-5 Function Assay 0.05-10 μM 24 h DMSO  reduces phosphorylated STAT3 levels 25646015
OVCAR-8 Function Assay 0.05-10 μM 24 h DMSO  reduces phosphorylated STAT3 levels 25646015
MOVCAR-5447 Function Assay 0.05-10 μM 24 h DMSO  reduces phosphorylated STAT3 levels 25646015
MOVCAR-5009 Function Assay 0.05-10 μM 24 h DMSO  reduces phosphorylated STAT3 levels 25646015
A1847 Cell Viability Assay 0.05-10 μM 72 h DMSO reduces cell viability at the concerntration of 5 μM 25646015
OVCAR-5 Cell Viability Assay 0.05-10 μM 72 h DMSO reduces cell viability at the concerntration of 5 μM 25646015
OVCAR-8  Cell Viability Assay 0.05-10 μM 72 h DMSO reduces cell viability at the concerntration of 5 μM 25646015
OVCAR-5  Apoptosis Assay 0.5/1/5 μM 48 h DMSO induces significant apoptosis at high concerntration 25646015
OVCAR-8  Apoptosis Assay 0.5/1/5 μM 48 h DMSO induces significant apoptosis at high concerntration 25646015
AKRSL Cell Viability Assay 72 h IC50＞10 μM 25504635
PALJDL Cell Viability Assay 72 h IC50=2.4 μM 25504635
MO4 Function Assay 0.5/1/5 μM 6 h inhibits P-STAT3 expression  25149535
DU145  Function Assay 0-200 nM 1 h  suppresses IL-6-activated Stat3 and ERK1/2 signaling 24577942
DU145  Function Assay 800 nM 72 h suppresses IL-6-induced migratory 24577942
CWR22Rv1 Function Assay 800 nM 72 h suppresses IL-6-induced migratory 24577942
N592 Growth Inhibition Assay IC50=0.84 μM 24158701
H82 Growth Inhibition Assay IC50=1.37 μM 24158701
GLC4 Growth Inhibition Assay IC50=1.79 μM 24158701
H526 Growth Inhibition Assay IC50=3.08 μM 24158701
H1173 Growth Inhibition Assay IC50=2.39 μM 24158701
DMS114 Growth Inhibition Assay IC50=0.73 μM 24158701
NCI-N592 Function Assay 0.3/1/3 μM 24 h induces G2/M cell cycle arrest 24158701
GLC4 Function Assay 0.3/1/3 μM 24 h induces G2/M cell cycle arrest 24158701
NCI-H82 Function Assay 0.3/1/3 μM 24 h induces G2/M cell cycle arrest 24158701
NCI-N592 Apoptosis Assay 0.3/1/3 μM 48 h increases the level of cleaved-Caspase 3 24158701
GLC4 Apoptosis Assay 0.3/1/3 μM 48 h increases the level of cleaved-Caspase 3 24158701
NCI-H82 Apoptosis Assay 0.3/1/3 μM 48 h increases the level of cleaved-Caspase 3 24158701
CWR22Rv1  Apoptosis Assay IC50=0.482 μM 23942095
CWR22Pc Apoptosis Assay IC50=0.438 μM 23942095
PC-3 Apoptosis Assay IC50=1.755 μM 23942095
DU145 Apoptosis Assay IC50=3.517 μM 23942095
RC165N Apoptosis Assay IC50=2.083 μM 23942095
ARPE19 Growth Inhibition Assay DMSO IC50=24.38 μM 23531921
HEK293 Growth Inhibition Assay DMSO IC50=8.67 μM 23531921
KCNR Growth Inhibition Assay DMSO IC50=0.46 μM 23531921
SY5Y Growth Inhibition Assay DMSO IC50=0.36 μM 23531921
BE2 Growth Inhibition Assay DMSO IC50=0.71 μM 23531921
AS Growth Inhibition Assay DMSO IC50=1.53 μM 23531921
NGP Growth Inhibition Assay DMSO IC50=0.56 μM 23531921
IMR32 Growth Inhibition Assay DMSO IC50=0.66 μM 23531921
LAN5 Growth Inhibition Assay DMSO IC50=1.04 μM 23531921
RH18 Growth Inhibition Assay DMSO IC50=1.42 μM 23531921
RH30 Growth Inhibition Assay DMSO IC50=1.25 μM 23531921
RH17 Growth Inhibition Assay DMSO IC50=2.51 μM 23531921
RH28 Growth Inhibition Assay DMSO IC50=4.28 μM 23531921
RH36 Growth Inhibition Assay DMSO IC50=5.37 μM 23531921
RH41 Growth Inhibition Assay DMSO IC50=0.48 μM 23531921
RD Growth Inhibition Assay DMSO IC50=4.32 μM 23531921
TC32 Growth Inhibition Assay DMSO IC50=3.85 μM 23531921
TC71 Growth Inhibition Assay DMSO IC50=4.33 μM 23531921
KCNR Apoptosis Assay 0.5/1.0/2.5 μM 24 h DMSO induces an increase in caspase 3/7 activity 23531921
SY5Y Apoptosis Assay 0.5/1.0/2.5 μM 24 h DMSO induces an increase in caspase 3/7 activity 23531921
Rh18 Apoptosis Assay 0.5/1.0/2.5 μM 24 h DMSO induces an increase in caspase 3/7 activity 23531921
TC32 Apoptosis Assay 0.5/1.0/2.5 μM 24 h DMSO induces an increase in caspase 3/7 activity 23531921
KCNR Function Assay 0.5/1.0/2.5/5 μM 24 h DMSO inhibits both endogenous constitutive and IL-6-induced STAT3 activation 23531921
SY5Y Function Assay 0.5/1.0/2.5/5 μM 24 h DMSO inhibits both endogenous constitutive and IL-6-induced STAT3 activation 23531921
Rh18 Function Assay 0.5/1.0/2.5/5 μM 24 h DMSO inhibits both endogenous constitutive and IL-6-induced STAT3 activation 23531921
TC32 Function Assay 0.5/1.0/2.5/5 μM 24 h DMSO inhibits both endogenous constitutive and IL-6-induced STAT3 activation 23531921
TPC-1 Growth Inhibition Assay 1 µM 0-4 d DMSO inhibits cell growth after 2 d treatment 23056499
MZ-CRC1  Growth Inhibition Assay 1 µM 0-5 d DMSO inhibits cell growth after 1 d treatment 23056499
TT  Growth Inhibition Assay 1 µM 0-4 d DMSO inhibits cell growth after 1 d treatment 23056499
TPC-1 Function Assay 1 µM 72 h DMSO induces G1 blockage 23056499
MZ-CRC1  Function Assay 1 µM 72 h DMSO induces G1 blockage 23056499
TT  Function Assay 1 µM 72 h DMSO induces G1 blockage 23056499
MZ-CRC1  Apoptosis Assay 1 µM 48 h DMSO induces apoptosis 23056499
TT  Apoptosis Assay 1 µM 48 h DMSO induces apoptosis 23056499
HD-LM2 Growth Inhibition Assay 72 h DMSO IC50=7.844 μM 22829094
L-428 Growth Inhibition Assay 72 h DMSO IC50=7.947 μM 22829094
KM-H2 Growth Inhibition Assay 72 h DMSO IC50=1.308 μM 22829094
L-540 Growth Inhibition Assay 72 h DMSO IC50=8.216 μM 22829094
HD-LM2 Function Assay 0.1/0.5/1/5 μM 72 h DMSO inhibits STAT3, STAT5 and STAT6 phosphorylation 22829094
L-428 Function Assay 0.1/0.5/1/5 μM 72 h DMSO inhibits STAT3, STAT5 and STAT6 phosphorylation 22829094
KM-H2 Function Assay 0.1/0.5/1/5 μM 72 h DMSO inhibits STAT3, STAT5 and STAT6 phosphorylation 22829094
L-540 Function Assay 0.1/0.5/1/5 μM 72 h DMSO inhibits STAT3, STAT5 and STAT6 phosphorylation 22829094
HD-LM2 Apoptosis Assay 1/5 μM 72 h DMSO induces apoptosis 22829094
L-428 Apoptosis Assay 1/5 μM 72 h DMSO induces apoptosis 22829094
KM-H2 Apoptosis Assay 1/5 μM 72 h DMSO induces apoptosis 22829094
L-540 Apoptosis Assay 1/5 μM 72 h DMSO induces apoptosis 22829094
U251-MG Function Assay 1 µM 0-16 h inhibits constitutive STAT-3 and JAK2 activation 22027691
U87-MG Function Assay 1 µM 0-16 h inhibits constitutive STAT-3 and JAK2 activation 22027691
4C8 Function Assay 1 µM 0-16 h inhibits constitutive STAT-3 and JAK2 activation 22027691
U251-MG Growth Inhibition Assay 1/10 µM 24/48/72 h inhibits cell proliferation at a concentration of 10 µM 22027691
U87-MG Growth Inhibition Assay 1/10 µM 24/48/72 h inhibits cell proliferation at a concentration of 10 µM 22027691
4C8 Growth Inhibition Assay 1/10 µM 24/48/72 h inhibits cell proliferation at a concentration of 10 µM 22027691
U266 Apoptosis Assay 0.5-2 μM 48/72 h induces apoptosis dose dependently 21164517
Kms.11 Apoptosis Assay 0.5-2 μM 48/72 h induces apoptosis dose dependently 21164517
8226 Apoptosis Assay 0.5-2 μM 48/72 h induces apoptosis dose dependently 21164517
SET2 Growth inhibition assay 48 hrs Growth inhibition of human SET2 cells expressing Jak2 V617F mutant after 48 hrs by MTS assay, GI50 = 0.016 μM. 21138246
SET2 Function assay 1 hr Inhibition of Stat3 phosphorylation in human SET2 cells after 1 hr by Western blotting, IC50 = 0.023 μM. 21138246
SET2 Function assay 1 hr Inhibition of Stat5 phosphorylation in human SET2 cells after 1 hr by Western blotting, IC50 = 0.025 μM. 21138246
HEL Function assay 1 hr Inhibition of Stat5 phosphorylation in human HEL cells after 1 hr by Western blotting, IC50 = 0.041 μM. 21138246
Ba/F3 Function assay Inhibition of Stat5 phosphorylation in mouse Ba/F3 cells expressing TEL-Jak2, IC50 = 0.046 μM. 21138246
UKE1 Growth inhibition assay 48 hrs Growth inhibition of human UKE1 cells expressing Jak2 V617F mutant after 48 hrs by MTS assay, GI50 = 0.054 μM. 21138246
BA/F3 Growth inhibition assay 48 hrs Growth inhibition of mouse BA/F3 cells expressing Tel-JAK2 kinase after 48 hrs by MTS assay, GI50 = 0.06 μM. 21138246
HEL Function assay 1 hr Inhibition of Stat3 phosphorylation in human HEL cells after 1 hr by Western blotting, IC50 = 0.08 μM. 21138246
HEL Growth inhibition assay 48 hrs Growth inhibition of human HEL cells expressing Jak2 V617F mutant after 48 hrs by MTS assay, GI50 = 0.39 μM. 21138246
BA/F3 Growth inhibition assay 48 hrs Growth inhibition of mouse BA/F3 cells expressing Tel-JAK1 kinase after 48 hrs by MTS assay, GI50 = 0.7 μM. 21138246
BA/F3 Growth inhibition assay 48 hrs Growth inhibition of mouse BA/F3 cells expressing Tel-Tyk2 kinase after 48 hrs by MTS assay, GI50 = 2 μM. 21138246
BA/F3 Growth inhibition assay 48 hrs Growth inhibition of mouse BA/F3 cells expressing Tel-JAK3 kinase after 48 hrs by MTS assay, GI50 = 2.1 μM. 21138246
UKE1 Function assay 1 hr Inhibition of Stat5 phosphorylation in human UKE1 cells after 1 hr by Western blotting 21138246
SW620 Cell cycle assay 3.3 uM 24 hrs Cell cycle arrest in human SW620 cells assessed as accumulation at G2/M phase at 3.3 uM after 24 hrs by flow cytometry 21138246
HEL Function assay 0.3 uM 5 mins Inhibition of Stat5 phosphorylation in human HEL cells at 0.3 uM after 5 mins by Western blotting 21138246
HEL Function assay 0.3 uM 30 to 60 mins Inhibition of Stat5 phosphorylation in human HEL cells at 0.3 uM after 30 to 60 mins by Western blotting 21138246
BA/F3 Antitumor assay 30 mg/kg 12 hrs Antitumor activity against mouse BA/F3 cells expressing Tel-JAK2 xenografted in NCr mouse assessed as reduction of phosphorylated Stat5 level in spleen at 30 mg/kg, po after 12 hrs by Western blotting 21138246
HEL Function assay 0.3 uM 5 mins Inhibition of Stat3 phosphorylation in human HEL cells at 0.3 uM after 5 mins by Western blotting 21138246
HEL Function assay 0.3 uM 30 to 60 mins Inhibition of Stat3 phosphorylation in human HEL cells at 0.3 uM after 30 to 60 mins by Western blotting 21138246
Hs578T Function assay 1 uM 24 hrs Inhibition of STAT3C-mediated transcription in human Hs578T cells at 1 uM after 24 hrs by luciferase reporter gene assay 24978112
NCI-H1975 Function assay 0.003 to 3 uM 2 hrs Inhibition of JAK1 in human NCI-H1975 cells assessed as reduction in STAT3 phosphorylation at 0.003 to 3 uM after 2 hrs by Western blot analysis 26614408
HEL 92.1.7 Function assay 2 hrs Inhibition of JAK2 in human HEL 92.1.7 cells assessed as reduction in STAT5 phosphorylation after 2 hrs by Western blot analysis 26614408
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
Saos-2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
BT-12 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
OHS-50 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description AZD1480 is a novel ATP-competitive JAK2 inhibitor with IC50 of 0.26 nM in a cell-free assay, selectivity against JAK3 and Tyk2, and to a smaller extent against JAK1. Phase 1.
Targets
JAK2 [1]
(Cell-free assay)
0.26 nM
In vitro
In vitro 5μM AZD1480 induces G2/M arrest and cell death by inhibiting Aurora kinases. [1] AZD1480 is a potent JAK2 inhibitor that can suppress growth, survival, as well as FGFR3 and STAT3 signaling and downstream targets including Cyclin D2 in human multiple myeloma cells. At low micromolar concentrations, AZD1480 blocks cell proliferation and induces apoptosis of myeloma cell lines. [2]AZD1480 effectively blocks constitutive and stimulus-induced JAK1, JAK2, and STAT-3 phosphorylation in both human and murine glioma cells, and leads to a decrease in cell proliferation and induction of apoptosis. [3]AZD1480 is a potent, competitive small-molecule inhibitor of JAK1/2 kinase, and that it is capable of inhibiting STAT3 phosphorylation and tumor growth in a STAT3-dependent manner. AZD1480 inhibits tumor angiogenesis and metastasis in part by affecting the tumor microenvironment. [4]
Kinase Assay kinase assays
Inhibition studies of AZD1480 are performed using recombinant Jak1, Jak2, or Jak3 under buffer conditions of 50 mM HEPES pH 7.3, 1 mM DTT, 0.01% Tween-20, 50 mM/ml BSA, and 10 mM MgCl2. Jak3 enzyme is expressed as N-terminal GST fusion in insect cells and purified by glutathione-affinity and size-exclusion chromatographies. Enzymes are assayed in the presence of AZD1480 (10 point dose response, in triplicate, from 8.3 μM to 0.3 nM in half-log dilution steps) using 1.5 μM peptide substrate (Jak1: FITC-C6-KKHTDDGYMPMSPGVA-NH2, Jak2 and Jak3: FAM-SRCtide) and screened under their respective ATP Km (Jak1: 55 μM, Jak2: 15 μM, Jak3: 3 μM) and approximated physiological ATP concentration of 5 mM. Phosphorylated and unphosphorylated peptides are separated and quantified by a Caliper LC3000 system for calculating percent inhibition.
Cell Research Cell lines Renca or 786-O cells, mouse endothelial cells and splenic CD11b+/c-myeloid cells, HUVECs
Concentrations ~1 μM
Incubation Time 48 or 24 hours
Method Renca or 786-O cells are suspended in DMEM medium with 5% FBS , and seeded in 96-well plates (5×103 per well) to allow adhesion and then treated with DMSO or AZD1480 for 48 hours. Cell viability is determined by MTS assay. Absorbance at 490 nm is measured with Mikrotek Laborsysteme. Mouse endothelial cells and splenic CD11b+/c- myeloid cells are enriched from tumor-bearing mice,and cultured in 5% FBS RPMI-1640 medium. HUVECs are cultured on collagen 1–coated plates in complete medium. All cells are treated with DMSO and AZD1480 at various doses for 24 hours. Cell viability is determined by counting cell number manually. All the experiments are repeated 3 times.
Experimental Result Images Methods Biomarkers Images PMID
Western blot p-STAT3 / STAT3 / p-JAK2 / JAK2 p-STAT1 / STAT1 / p-STAT5 / STAT5 / p-STAT6 / STAT6 p-ERK / ERK / p-p38 / p38 / SOCS3 / p-SHP2 / SHP2 22027691
Immunofluorescence pSTAT5 30140255
Growth inhibition assay Cell proliferation Cell viability 22027691
In Vivo
In vivo AZD1480 inhibits the STAT3 phosphorylation in an xenograft model of human solid tumors and multiple myeloma. [1] In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial glioblastoma (GBM) tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered for study in the treatment of patients with GBM tumors. [3]AZD1480 blocks lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduces angiogenesis and metastasis in a human xenograft tumor model. [4] The Jak2 inhibitor, AZD1480, suppresses the growth of human solid tumor xenografts harboring persistent Stat3 activity. [5]
Animal Research Animal Models Female BALB/c and athymic nude (NCR - nu/nu) mice (7–8 weeks old)
Dosages Once a day at the dose of 50 mg/kg or twice daily at 30 mg/kg
Administration Oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01219543 Terminated
Solid Tumour|Advanced Solid Malignancies|Child-Pugh A to B7 Advanced Hepatocellular Carcinoma|EGFR and/or ROS Mutant NSCLC|Lung Metastasis Carcinoma|Gastric Cancer
AstraZeneca
 November 2010 Phase 1
NCT01112397 Terminated
Solid Malignancies
AstraZeneca
 April 2010 Phase 1

Chemical Information & Solubility

Molecular Weight 348.77 Formula

C14H14ClFN8
CAS No. 935666-88-9 SDF Download AZD1480 SDF
Smiles CC1=CC(=NN1)NC2=NC(=NC=C2Cl)NC(C)C3=NC=C(C=N3)F
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 69 mg/mL ( (197.83 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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