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| 25mg |
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| 100mg |
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Purity: ≥98%
AZD1480 (AZD-1480) is a selective, orally bioavailable and ATP-competitive inhibitor of JAK2 (Janus-associated kinase) with potential antitumor activity. It inhibits JAK2 with an IC50 of 0.26 nM in a cell-free assay. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy, because JAK2 is upregulated/mutated in a variety of cancer cells, mediating STAT3 activation and playing a key role in tumor cell proliferation and survival.
| ln Vitro |
By blocking Aurora kinase, AZD-1480 (5 μM) causes G2/M arrest and cell death [1]. Strongly inhibiting proliferation, survival, FGFR3 and STAT3 signaling, as well as downstream targets such cyclin D2, in human multiple myeloma cells is AZD-1480. In myeloma cell lines, AZD-1480 causes apoptosis and inhibits cell proliferation at low micromolar doses [2]. In human and mouse glioma cells, AZD-1480 can efficiently inhibit constitutive and stimulus-induced phosphorylation of JAK1, JAK2, and STAT-3, which reduces cell proliferation and induces apoptosis [3]. As a strong competitive small molecule inhibitor of JAK1/2 kinase, AZD-1480 reduces tumor development and STAT3 phosphorylation in a manner that is dependent on STAT3. By altering the tumor microenvironment, AZD-1480 partially prevents tumor angiogenesis and metastasis [4].
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| ln Vivo |
In multiple myeloma xenograft models and human solid tumors, AZD-1480 suppresses STAT3 phosphorylation [1]. AZD-1480 prolongs mouse life in vivo by preventing subcutaneous tumors from growing. By suppressing STAT-3 activity, it prevents intracranial glioblastoma (GBM) tumors, indicating AZD-1480's impact on the JAK/STAT-3 pathway. In research involving patients with GBM tumors, pharmacological inhibition must to be taken into account [3]. AZD-1480 prevents myeloid cell infiltration into the lungs and the development of lung metastases in models of spontaneous metastasis and syngeneic experimental mice. In addition, AZD-1480 decreases metastasis and angiogenesis in tumor models derived from human xenografts [4]. Human solid tumor xenografts with prolonged Stat3 activation are not able to grow when exposed to AZD-1480 [5].
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| Animal Protocol |
SCID/Beige mice injected with TC32 or Rh18 cells;
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| References | |
| Additional Infomation |
AZD1480 has been used in trials studying the treatment of Solid Malignancies, Post-Polycythaemia Vera, Primary Myelofibrosis (PMF), and Essential Thrombocythaemia Myelofibrosis.
JAK2 Inhibitor AZD1480 is an orally bioavailable inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. JAK2 inhibitor AZD1480 inhibits JAK2 activation, leading to the inhibition of the JAK/STAT (signal transducer and activator of transcription) signaling including activation of STAT3. This may lead to induction of tumor cell apoptosis and a decrease in cellular proliferation. JAK2, often upregulated or mutated in a variety of cancer cells, mediates STAT3 activation and plays a key role in tumor cell proliferation and survival. |
| Molecular Formula |
C14H14CLFN8
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|---|---|
| Molecular Weight |
348.7660
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| Exact Mass |
348.101
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| CAS # |
935666-88-9
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| PubChem CID |
16659841
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| Appearance |
White to yellow solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
575.2±60.0 °C at 760 mmHg
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| Flash Point |
301.7±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.702
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
24
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| Complexity |
397
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CC(=NN1)NC2=NC(=NC=C2Cl)N[C@@H](C)C3=NC=C(C=N3)F
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| InChi Key |
PDOQBOJDRPLBQU-QMMMGPOBSA-N
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| InChi Code |
InChI=1S/C14H14ClFN8/c1-7-3-11(24-23-7)21-13-10(15)6-19-14(22-13)20-8(2)12-17-4-9(16)5-18-12/h3-6,8H,1-2H3,(H3,19,20,21,22,23,24)/t8-/m0/s1
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| Chemical Name |
(S)-5-chloro-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine
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| Synonyms |
AZD-1480; AZD1480; AZD 1480
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~143.36 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.17 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8672 mL | 14.3361 mL | 28.6722 mL | |
| 5 mM | 0.5734 mL | 2.8672 mL | 5.7344 mL | |
| 10 mM | 0.2867 mL | 1.4336 mL | 2.8672 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01219543 | Terminated | Drug: AZD1480 Daily Drug: AZD1480 BID |
Solid Tumour Advanced Solid Malignancies |
AstraZeneca | November 2010 | Phase 1 |
| NCT01112397 | Terminated | Drug: AZD1480 | Solid Malignancies | AstraZeneca | April 2010 | Phase 1 |
| NCT00910728 | Completed Has Results | Drug: AZD1480 | Primary Myelofibrosis (PMF) Post-Polycythaemia Vera |
AstraZeneca | August 23, 2017 | Phase 1 |
AZD1480 inhibits spontaneous lung metastasis of mouse syngeneic tumors.Cancer Res.2011 Nov 1;71(21):6601-10. |
AZD1480 inhibits experimental lung metastasis of mouse syngeneic tumors.Cancer Res.2011 Nov 1;71(21):6601-10. |
AZD1480 inhibits angiogenesis and metastasis in 786-O xenografts and over-expression of constitutively active STAT3 rescues 786-O tumor from angiogenic inhibition.Cancer Res.2011 Nov 1;71(21):6601-10. |
Baseline JAK/STAT pathway activation status and effects of AZD1480 in HL cell lines.Blood Cancer J.2011 Dec;1(12):e46. |
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AZD1480 induces paradoxical hyperphosphorylation of JAK2, TYK2 and MAP Kinases (ERK, p38) in HL cells.Blood Cancer J.2011 Dec;1(12):e46. |
AZD1480 induces G2/M cell cycle arrest by inhibition of Aurora A in HL cell lines.Blood Cancer J.2011 Dec;1(12):e46. |
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