AZD-1480

WARNING: This product is for research use only, not for human or veterinary use.

Description: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.

Price and Availability

AZD-1480 , purity > 98%, isout of stock

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 204510Name: AZD-1480CAS#: 935666-88-9Chemical Formula: C14H14ClFN8Exact Mass: 348.1014Molecular Weight: 348.76596Elemental Analysis:C, 48.21; H, 4.05; Cl, 10.17; F, 5.45; N, 32.13

Synonym:AZD1480; AZD-1480; AZD 1480

IUPAC/Chemical Name:(S)-5-chloro-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine

InChi Key:PDOQBOJDRPLBQU-QMMMGPOBSA-N

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

SMILES Code:CC1=CC(NC2=NC(N[C@H](C3=NC=C(F)C=N3)C)=NC=C2Cl)=NN1

Technical Data

Additional Information

AZD1480 inhibits STAT3 in tumor-associated myeloid cells, reducing their number and inhibiting tumor metastasis. Myeloid cell-mediated angiogenesis was also diminished by AZD1480, with additional direct inhibition of endothelial cell function in vitro and in vivo. AZD1480 blocked lung infiltration of myeloid cells and formation of pulmonary metastases in both mouse syngeneic experimental and spontaneous metastatic models. Furthermore, AZD1480 reduced angiogenesis and metastasis in a human xenograft tumor model. Although the effects of AZD1480 on the tumor microenvironment were important for the observed antiangiogenic activity, constitutive activation of STAT3 in tumor cells themselves could block these antiangiogenic effects, showing the complexity of the JAK/STAT signaling network in tumor progression. Together, AZD1480 can effectively inhibit tumor angiogenesis and metastasis mediated by STAT3 in stromal cells as well as tumor cells. (source: Cancer Res. 2011 Nov 1;71(21):6601-10.)  

References

1: Liu Y, Holdbrooks AT, De Sarno P, Rowse AL,Yanagisawa LL, McFarland BC, Harrington LE, Raman C, Sabbaj S,Benveniste EN, Qin H. Therapeutic efficacy of suppressing the Jak/STATpathway in multiple models of experimental autoimmune encephalomyelitis.J Immunol. 2014 Jan 1;192(1):59-72. doi: 10.4049/jimmunol.1301513. Epub2013 Dec 9. PubMed PMID: 24323580; PubMed Central PMCID: PMC3934829.

2: Sun ZL, Tang YJ, Wu WG, Xing J, He YF, Xin DM, Yu YL, Yang Y, Han P.AZD1480 can inhibit the biological behavior of ovarian cancer SKOV3cells in vitro. Asian Pac J Cancer Prev. 2013;14(8):4823-7. PubMed PMID:24083752.

3: Gu L, Liao Z, Hoang DT, Dagvadorj A, Gupta S, Blackmon S, EllsworthE, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, GomellaL, Huszar D, Nevalainen MT. Pharmacologic inhibition of Jak2-Stat5signaling By Jak2 inhibitor AZD1480 potently suppresses growth of bothprimary and castrate-resistant prostate cancer. Clin Cancer Res. 2013Oct 15;19(20):5658-74. doi: 10.1158/1078-0432.CCR-13-0422. Epub 2013 Aug13. PubMed PMID: 23942095.

4: Plimack ER, Lorusso PM, McCoon P, Tang W, Krebs AD, Curt G, EckhardtSG. AZD1480: a phase I study of a novel JAK2 inhibitor in solid tumors.Oncologist. 2013;18(7):819-20. doi: 10.1634/theoncologist.2013-0198.Epub 2013 Jul 11. PubMed PMID: 23847256; PubMed Central PMCID:PMC3720635.

5: Chang Q, Bournazou E, Sansone P, Berishaj M, Gao SP, Daly L, Wels J,Theilen T, Granitto S, Zhang X, Cotari J, Alpaugh ML, de Stanchina E,Manova K, Li M, Bonafe M, Ceccarelli C, Taffurelli M, Santini D, Altan-BonnetG, Kaplan R, Norton L, Nishimoto N, Huszar D, Lyden D, Bromberg J. TheIL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis.Neoplasia. 2013 Jul;15(7):848-62. PubMed PMID: 23814496; PubMed CentralPMCID: PMC3689247.

6: Yan S, Li Z, Thiele CJ. Inhibition of STAT3 with orally active JAKinhibitor, AZD1480, decreases tumor growth in Neuroblastoma andPediatric Sarcomas In vitro and In vivo. Oncotarget. 2013Mar;4(3):433-45. PubMed PMID: 23531921; PubMed Central PMCID:PMC3717306.

7: Bogani C, Bartalucci N, Martinelli S, Tozzi L, Guglielmelli P, BosiA, Vannucchi AM; Associazione Italiana per la Ricerca sul Cancro AGIMMGruppo Italiano Malattie Mieloproliferative. mTOR inhibitors alone andin combination with JAK2 inhibitors effectively inhibit cells ofmyeloproliferative neoplasms. PLoS One. 2013;8(1):e54826. doi:10.1371/journal.pone.0054826. Epub 2013 Jan 31. PubMed PMID: 23382981;PubMed Central PMCID: PMC3561413.

8: Couto JP, Almeida A, Daly L, Sobrinho-Simões M, Bromberg JF, SoaresP. AZD1480 blocks growth and tumorigenesis of RET- activated thyroidcancer cell lines. PLoS One. 2012;7(10):e46869. doi:10.1371/journal.pone.0046869. Epub 2012 Oct 2. PubMed PMID: 23056499;PubMed Central PMCID: PMC3462763.

9: de Groot J, Liang J, Kong LY, Wei J, Piao Y, Fuller G, Qiao W,Heimberger AB. Modulating antiangiogenic resistance by inhibiting thesignal transducer and activator of transcription 3 pathway inglioblastoma. Oncotarget. 2012 Sep;3(9):1036-48. PubMed PMID: 23013619;PubMed Central PMCID: PMC3660053.

10: Loveless ME, Lawson D, Collins M, Nadella MV, Reimer C, Huszar D,Halliday J, Waterton JC, Gore JC, Yankeelov TE. Comparisons of theefficacy of a Jak1/2 inhibitor (AZD1480) with a VEGF signaling inhibitor(cediranib) and sham treatments in mouse tumors using DCE-MRI, DW-MRI,and histology. Neoplasia. 2012 Jan;14(1):54-64. PubMed PMID: 22355274;PubMed Central PMCID: PMC3281942.