Fedratinib (TG101348)
Fedratinib, also known as TG101348 and SAR302503, is a JAK2 inhibitor, is also an orally bioavailable, small-molecule, ATP-competitive inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. JAK2 inhibitor TG101348 competes with JAK2 as well as the mutated form AK2V617F for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and the induction of tumor cell apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders (MPDs); the mutated form JAK2V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.
1: Stein BL, Crispino JD, Moliterno AR. Janus kinase inhibitors: an update on the progress and promise of targeted therapy in the myeloproliferative neoplasms. Curr Opin Oncol. 2011 Nov;23(6):609-16. Review. PubMed PMID: 21993415.
2: Deshpande A, Reddy MM, Schade GO, Ray A, Chowdary TK, Griffin JD, Sattler M. Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia. 2011 Sep 16. doi: 10.1038/leu.2011.255. [Epub ahead of print] PubMed PMID: 21926964.
3: Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW. Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen. Blood. 2011 Nov 10;118(19):5330-9. Epub 2011 Sep 13. PubMed PMID: 21917753; PubMed Central PMCID: PMC3217413.
4: Looi CY, Imanishi M, Takaki S, Sato M, Chiba N, Sasahara Y, Futaki S, Tsuchiya S, Kumaki S. Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis. PLoS One. 2011;6(8):e23640. Epub 2011 Aug 10. PubMed PMID: 21853157; PubMed Central PMCID: PMC3154509.
5: Passamonti F, Maffioli M, Caramazza D, Cazzola M. Myeloproliferative neoplasms: from JAK2 mutations discovery to JAK2 inhibitor therapies. Oncotarget. 2011 Jun;2(6):485-90. PubMed PMID: 21646683.
6: Pardanani A, Tefferi A. Targeting myeloproliferative neoplasms with JAK inhibitors. Curr Opin Hematol. 2011 Mar;18(2):105-10. Review. PubMed PMID: 21245760.
7: Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, Silverman MH, Gilliland DG, Shorr J, Tefferi A. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011 Mar 1;29(7):789-96. Epub 2011 Jan 10. PubMed PMID: 21220608.
8: Pardanani A, Vannucchi AM, Passamonti F, Cervantes F, Barbui T, Tefferi A. JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia. 2011 Feb;25(2):218-25. Epub 2010 Nov 16. Review. PubMed PMID: 21079613.
9: Mullally A, Lane SW, Ball B, Megerdichian C, Okabe R, Al-Shahrour F, Paktinat M, Haydu JE, Housman E, Lord AM, Wernig G, Kharas MG, Mercher T, Kutok JL, Gilliland DG, Ebert BL. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell. 2010 Jun 15;17(6):584-96. PubMed PMID: 20541703; PubMed Central PMCID: PMC2909585.
10: Cotto M, Cabanillas F, Tirado M, GarcÃa MV, Pacheco E. Epigenetic therapy of lymphoma using histone deacetylase inhibitors. Clin Transl Oncol. 2010 Jun;12(6):401-9. Review. PubMed PMID: 20534395.
2: Deshpande A, Reddy MM, Schade GO, Ray A, Chowdary TK, Griffin JD, Sattler M. Kinase domain mutations confer resistance to novel inhibitors targeting JAK2V617F in myeloproliferative neoplasms. Leukemia. 2011 Sep 16. doi: 10.1038/leu.2011.255. [Epub ahead of print] PubMed PMID: 21926964.
3: Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW. Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen. Blood. 2011 Nov 10;118(19):5330-9. Epub 2011 Sep 13. PubMed PMID: 21917753; PubMed Central PMCID: PMC3217413.
4: Looi CY, Imanishi M, Takaki S, Sato M, Chiba N, Sasahara Y, Futaki S, Tsuchiya S, Kumaki S. Octa-arginine mediated delivery of wild-type Lnk protein inhibits TPO-induced M-MOK megakaryoblastic leukemic cell growth by promoting apoptosis. PLoS One. 2011;6(8):e23640. Epub 2011 Aug 10. PubMed PMID: 21853157; PubMed Central PMCID: PMC3154509.
5: Passamonti F, Maffioli M, Caramazza D, Cazzola M. Myeloproliferative neoplasms: from JAK2 mutations discovery to JAK2 inhibitor therapies. Oncotarget. 2011 Jun;2(6):485-90. PubMed PMID: 21646683.
6: Pardanani A, Tefferi A. Targeting myeloproliferative neoplasms with JAK inhibitors. Curr Opin Hematol. 2011 Mar;18(2):105-10. Review. PubMed PMID: 21245760.
7: Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, Silverman MH, Gilliland DG, Shorr J, Tefferi A. Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol. 2011 Mar 1;29(7):789-96. Epub 2011 Jan 10. PubMed PMID: 21220608.
8: Pardanani A, Vannucchi AM, Passamonti F, Cervantes F, Barbui T, Tefferi A. JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia. 2011 Feb;25(2):218-25. Epub 2010 Nov 16. Review. PubMed PMID: 21079613.
9: Mullally A, Lane SW, Ball B, Megerdichian C, Okabe R, Al-Shahrour F, Paktinat M, Haydu JE, Housman E, Lord AM, Wernig G, Kharas MG, Mercher T, Kutok JL, Gilliland DG, Ebert BL. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell. 2010 Jun 15;17(6):584-96. PubMed PMID: 20541703; PubMed Central PMCID: PMC2909585.
10: Cotto M, Cabanillas F, Tirado M, GarcÃa MV, Pacheco E. Epigenetic therapy of lymphoma using histone deacetylase inhibitors. Clin Transl Oncol. 2010 Jun;12(6):401-9. Review. PubMed PMID: 20534395.
| Chemical | |
|---|---|
| CAS Num | 936091-26-8 |
| Chemical Formula | C27H36N6O3S |
| Molecular Weight | 524.67814 |
| IUPAC Chemical Name | N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide |
| Exact Mass | 524.25696 |
| Elemental Analysis | C, 61.81; H, 6.92; N, 16.02; O, 9.15; S, 6.11 |
| Synonym | TG101348; TG 101348; TG-101348; SAR302503; SAR-302503; SAR 302503; Fedratinib. |
| Solubility | Soluble in DMSO, not in water |
| SMILES Code | O=S(C1=CC=CC(NC2=NC(NC3=CC=C(OCCN4CCCC4)C=C3)=NC=C2C)=C1)(NC(C)(C)C)=O |
| Biological | |
| Targets and Effects | JAK2 inhibitor |
| Pathways | Apoptosis |
| Physical | |
| Appearance | 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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