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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 |
[1]. Derenzini E, et al. The JAK inhibitor AZD1480 regulates proliferation and immunity in Hodgkin lymphoma. Blood Cancer J. 2011 Dec;1(12):e46.
[2]. Scuto A, et al. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia. 2011 Mar;25(3):538-50. [3]. McFarland BC, et al. Therapeutic potential of AZD1480 for the treatment of human glioblastoma. Mol Cancer Ther. 2011 Dec;10(12):2384-93. [4]. Xin H, et al. Antiangiogenic and antimetastatic activity of JAK inhibitor AZD1480. Cancer Res. 2011 Nov 1;71(21):6601-10. [5]. Hedvat M, et al. The JAK2 inhibitor AZD1480 potently blocks Stat3 signaling and oncogenesis in solid tumors. Cancer Cell. 2009 Dec 8;16(6):487-9 [6]. Ni J, et al. Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol. 2017 Jan;19(1):22-30 |
| Molecular Formula |
C14H14CLFN8
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|---|---|
| Molecular Weight |
348.7660
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| CAS # |
935666-88-9
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| SMILES |
CC1=CC(NC2=NC(N[C@H](C3=NC=C(F)C=N3)C)=NC=C2Cl)=NN1
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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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| 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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| 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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