Fedratinib

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

Description:Fedratinib, also known as TG101348 andSAR302503, 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.

Price and Availability

Fedratinib, purity > 98%, is in stock.The same day shipping out after order is received.

Chemical Structure

Theoretical Analysis

MedKoo Cat#: 202893Name: FedratinibCAS#: 936091-26-8 (free base)Chemical Formula: C27H36N6O3SExact Mass: 524.25696Molecular Weight: 524.67814Elemental Analysis:C, 61.81; H, 6.92; N, 16.02; O, 9.15; S, 6.11

Related CAS #:936091-26-8 (free base)1374744-69-0 (HCl hydrate)

Synonym:TG101348; TG 101348; TG-101348; SAR302503; SAR-302503; SAR 302503; Fedratinib.

IUPAC/Chemical Name:N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide

InChi Key:JOOXLOJCABQBSG-UHFFFAOYSA-N

InChi Code:InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)

SMILES Code:O=S(C1=CC=CC(NC2=NC(NC3=CC=C(OCCN4CCCC4)C=C3)=NC=C2C)=C1)(NC(C)(C)C)=O

Technical Data

Additional Information

References

1: Blair HA. Fedratinib: First Approval. Drugs. 2019 Oct;79(15):1719-1725. doi: 10.1007/s40265-019-01205-x. Review. PubMed PMID: 31571162.

2: Singer JW, Al-Fayoumi S, Taylor J, Velichko S, O"Mahony A. Comparative phenotypic profiling of the JAK2 inhibitors ruxolitinib, fedratinib, momelotinib, and pacritinib reveals distinct mechanistic signatures. PLoS One. 2019 Sep 27;14(9):e0222944. doi: 10.1371/journal.pone.0222944. eCollection 2019. PubMed PMID: 31560729; PubMed Central PMCID: PMC6764664.

3: Fedratinib Becomes New Option in Myelofibrosis. Cancer Discov. 2019 Oct;9(10):1332. doi: 10.1158/2159-8290.CD-NB2019-102. Epub 2019 Aug 30. PubMed PMID: 31471287.

4: Ogasawara K, Zhou S, Krishna G, Palmisano M, Li Y. Population pharmacokinetics of fedratinib in patients with myelofibrosis, polycythemia vera, and essential thrombocythemia. Cancer Chemother Pharmacol. 2019 Oct;84(4):891-898. doi: 10.1007/s00280-019-03929-9. Epub 2019 Aug 23. PubMed PMID: 31444617; PubMed Central PMCID: PMC6768916.

5: Chen D, Zhang F, Wang J, He H, Duan S, Zhu R, Chen C, Yin L, Chen Y. Biodegradable Nanoparticles Mediated Co-delivery of Erlotinib (ELTN) and Fedratinib (FDTN) Toward the Treatment of ELTN-Resistant Non-small Cell Lung Cancer (NSCLC) via Suppression of the JAK2/STAT3 Signaling Pathway. Front Pharmacol. 2018 Nov 13;9:1214. doi: 10.3389/fphar.2018.01214. eCollection 2018. PubMed PMID: 30483119; PubMed Central PMCID: PMC6242943.

6: Correction to "Interaction of 2,4-Diaminopyrimidine Containing Drugs Including Fedratinib and Trimethoprim with Thiamine Transporters". Drug Metab Dispos. 2017Nov;45(11):1146-1147. doi: 10.1124/dmd.116.073338err. PubMed PMID: 28974558.

7: Harrison CN, Schaap N, Vannucchi AM, Kiladjian JJ, Tiu RV, Zachee P, Jourdan E, Winton E, Silver RT, Schouten HC, Passamonti F, Zweegman S, Talpaz M, Lager J, Shun Z, Mesa RA. Janus kinase-2 inhibitor fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA-2): a single-arm, open-label, non-randomised, phase 2, multicentre study. Lancet Haematol. 2017 Jul;4(7):e317-e324. doi: 10.1016/S2352-3026(17)30088-1. Epub 2017 Jun 8. PubMed PMID: 28602585.

8: Hazell AS, Afadlal S, Cheresh DA, Azar A. Treatment of rats with the JAK-2 inhibitor fedratinib does not lead to experimental Wernicke"s encephalopathy. Neurosci Lett. 2017 Mar 6;642:163-167. doi: 10.1016/j.neulet.2017.01.041. Epub 2017 Jan 18. PubMed PMID: 28109775.

9: Giacomini MM, Hao J, Liang X, Chandrasekhar J, Twelves J, Whitney JA, Lepist EI, Ray AS. Interaction of 2,4-Diaminopyrimidine-Containing Drugs Including Fedratinib and Trimethoprim with Thiamine Transporters. Drug Metab Dispos. 2017 Jan;45(1):76-85. Epub 2016 Nov 1. Erratum in: Drug Metab Dispos. 2017 Nov;45(11):1146-1147. PubMed PMID: 27803021.

10: Zhang M, Xu C, Ma L, Shamiyeh E, Yin J, von Moltke LL, Smith WB. Effect of food on the bioavailability and tolerability of the JAK2-selective inhibitor fedratinib (SAR302503): Results from two phase I studies in healthy volunteers. Clin Pharmacol Drug Dev. 2015 Jul;4(4):315-21. doi: 10.1002/cpdd.161. Epub 2014 Oct 27. PubMed PMID: 27136912.

11: Jamieson C, Hasserjian R, Gotlib J, Cortes J, Stone R, Talpaz M, Thiele J, Rodig S, Pozdnyakova O. Effect of treatment with a JAK2-selective inhibitor, fedratinib, on bone marrow fibrosis in patients with myelofibrosis. J Transl Med. 2015 Sep 10;13:294. doi: 10.1186/s12967-015-0644-4. PubMed PMID: 26357842; PubMed Central PMCID: PMC4566296.

12: Pardanani A, Tefferi A, Jamieson C, Gabrail NY, Lebedinsky C, Gao G, Liu F, Xu C, Cao H, Talpaz M. A phase 2 randomized dose-ranging study of the JAK2-selective inhibitor fedratinib (SAR302503) in patients with myelofibrosis. Blood Cancer J. 2015 Aug 7;5:e335. doi: 10.1038/bcj.2015.63. PubMed PMID: 26252788; PubMed Central PMCID: PMC4558588.

13: Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, MassziT, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, Tefferi A. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2015 Aug;1(5):643-51. doi: 10.1001/jamaoncol.2015.1590. PubMed PMID: 26181658.

14: Polverelli N, Catani L, Vianelli N, Baccarani M, Cavo M, Palandri F. Ruxolitinib- but not fedratinib-induced extreme thrombocytosis: the combination therapy with hydroxyurea and ruxolitinib is effective in reducing platelet countand splenomegaly/constitutional symptoms. Ann Hematol. 2015 Sep;94(9):1585-7. doi: 10.1007/s00277-015-2397-9. Epub 2015 May 16. PubMed PMID: 25975976.

15: Zhang Q, Zhang Y, Diamond S, Boer J, Harris JJ, Li Y, Rupar M, Behshad E, Gardiner C, Collier P, Liu P, Burn T, Wynn R, Hollis G, Yeleswaram S. The Janus kinase 2 inhibitor fedratinib inhibits thiamine uptake: a putative mechanism forthe onset of Wernicke"s encephalopathy. Drug Metab Dispos. 2014 Oct;42(10):1656-62. doi: 10.1124/dmd.114.058883. Epub 2014 Jul 25. PubMed PMID: 25063672.

16: Zhang M, Xu CR, Shamiyeh E, Liu F, Yin JY, von Moltke LL, Smith WB. A randomized, placebo-controlled study of the pharmacokinetics, pharmacodynamics, and tolerability of the oral JAK2 inhibitor fedratinib (SAR302503) in healthy volunteers. J Clin Pharmacol. 2014 Apr;54(4):415-21. doi: 10.1002/jcph.218. Epub2013 Nov 16. PubMed PMID: 24165976.