AZD-1480
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.
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/STAT pathway in multiple models of experimental autoimmune encephalomyelitis. J Immunol. 2014 Jan 1;192(1):59-72. doi: 10.4049/jimmunol.1301513. Epub 2013 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 SKOV3 cells 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, Ellsworth E, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Huszar D, Nevalainen MT. Pharmacologic inhibition of Jak2-Stat5 signaling By Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer. Clin Cancer Res. 2013 Oct 15;19(20):5658-74. doi: 10.1158/1078-0432.CCR-13-0422. Epub 2013 Aug 13. PubMed PMID: 23942095.
4: Plimack ER, Lorusso PM, McCoon P, Tang W, Krebs AD, Curt G, Eckhardt SG. 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-Bonnet G, Kaplan R, Norton L, Nishimoto N, Huszar D, Lyden D, Bromberg J. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia. 2013 Jul;15(7):848-62. PubMed PMID: 23814496; PubMed Central PMCID: PMC3689247.
6: Yan S, Li Z, Thiele CJ. Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in Neuroblastoma and Pediatric Sarcomas In vitro and In vivo. Oncotarget. 2013 Mar;4(3):433-45. PubMed PMID: 23531921; PubMed Central PMCID: PMC3717306.
7: Bogani C, Bartalucci N, Martinelli S, Tozzi L, Guglielmelli P, Bosi A, Vannucchi AM; Associazione Italiana per la Ricerca sul Cancro AGIMM Gruppo Italiano Malattie Mieloproliferative. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative 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, Soares P. AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer 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 the signal transducer and activator of transcription 3 pathway in glioblastoma. 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 the efficacy 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.
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 SKOV3 cells 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, Ellsworth E, Talati P, Leiby B, Zinda M, Lallas CD, Trabulsi EJ, McCue P, Gomella L, Huszar D, Nevalainen MT. Pharmacologic inhibition of Jak2-Stat5 signaling By Jak2 inhibitor AZD1480 potently suppresses growth of both primary and castrate-resistant prostate cancer. Clin Cancer Res. 2013 Oct 15;19(20):5658-74. doi: 10.1158/1078-0432.CCR-13-0422. Epub 2013 Aug 13. PubMed PMID: 23942095.
4: Plimack ER, Lorusso PM, McCoon P, Tang W, Krebs AD, Curt G, Eckhardt SG. 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-Bonnet G, Kaplan R, Norton L, Nishimoto N, Huszar D, Lyden D, Bromberg J. The IL-6/JAK/Stat3 feed-forward loop drives tumorigenesis and metastasis. Neoplasia. 2013 Jul;15(7):848-62. PubMed PMID: 23814496; PubMed Central PMCID: PMC3689247.
6: Yan S, Li Z, Thiele CJ. Inhibition of STAT3 with orally active JAK inhibitor, AZD1480, decreases tumor growth in Neuroblastoma and Pediatric Sarcomas In vitro and In vivo. Oncotarget. 2013 Mar;4(3):433-45. PubMed PMID: 23531921; PubMed Central PMCID: PMC3717306.
7: Bogani C, Bartalucci N, Martinelli S, Tozzi L, Guglielmelli P, Bosi A, Vannucchi AM; Associazione Italiana per la Ricerca sul Cancro AGIMM Gruppo Italiano Malattie Mieloproliferative. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative 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, Soares P. AZD1480 blocks growth and tumorigenesis of RET- activated thyroid cancer 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 the signal transducer and activator of transcription 3 pathway in glioblastoma. 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 the efficacy 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.
| Chemical | |
|---|---|
| CAS Num | 935666-88-9 |
| Chemical Formula | C14H14ClFN8 |
| Molecular Weight | 348.76596 |
| IUPAC Chemical Name | (S)-5-chloro-N2-(1-(5-fluoropyrimidin-2-yl)ethyl)-N4-(5-methyl-1H-pyrazol-3-yl)pyrimidine-2,4-diamine |
| Exact Mass | 348.1014 |
| Elemental Analysis | C, 48.21; H, 4.05; Cl, 10.17; F, 5.45; N, 32.13 |
| Synonym | AZD1480; AZD-1480; AZD 1480 |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | CC1=CC(NC2=NC(N[C@H](C3=NC=C(F)C=N3)C)=NC=C2Cl)=NN1 |
| Biological | |
| Targets and Effects | JAK2 inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | white solid powder |
| Purity | >98% (or refer to the Certificate of Analysis) |
| Shipping Condition | Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs. |
| Storage Condition | Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years). |
| Shelf Life | >2 years if stored properly |
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