Fedratinib, sold under the brand name Inrebic, is an anti-cancer medication used to treat myeloproliferative diseases including myelofibrosis.[5] It is used in the form of fedratinib hydrochloride capsules that are taken by mouth. It is a semi-selective inhibitor of Janus kinase 2 (JAK-2).[5][6] It was approved by the FDA on 16 August 2019.[5]
Myelofibrosis is a myeloid cancer associated with anemia, splenomegaly, and constitutional symptoms. Patients with myelofibrosis frequently harbor mutations which activate the JAK-STAT signaling pathway and which are sensitive to fedratinib. Phase I trial results focused on safety and efficacy of fedratinib in patients with high- or intermediate-risk primary or post–polycythemia vera/essential thrombocythemia myelofibrosis have been published in 2011.[7]
In the European Union, fedratinib is indicated for the treatment of disease-related splenomegaly or symptoms in adults with primary myelofibrosis, following polycythaemia vera or essential thrombocythaemia, who are Janus kinase (JAK) inhibitor naïve or have been treated with ruxolitinib.[3]
Pharmacologyedit
Mechanism of actionedit
Fedratinib acts as a competitive inhibitor of protein kinase JAK-2 with IC50=6 nM; related kinases FLT3 and RET are also sensitive, with IC50=25 nM and IC50=17 nM, respectively. Significantly less activity was observed against other tyrosine kinases including JAK3 (IC50=169 nM).[8] In treated cells the inhibitor blocks downstream cellular signalling (JAK-STAT) leading to suppression of proliferation and induction of apoptosis.
Historyedit
Fedratinib was originally discovered at TargeGen. In 2010, Sanofi-Aventis acquired TargeGen and continued development of fedratinib until 2013. In 2016, Impact Biomedicines acquired the rights to fedratinib from Sanofi and continued its development for the treatment of myelofibrosis and polycythemia vera. In January 2018, the drug's rights were transferred to Celgene with their purchase of Impact Biomedicines.[9]
Fedratinib was approved for medical use in the United States in August 2019.[2][5][6]
The U.S. Food and Drug Administration (FDA) granted the application for fedratinib priority review and orphan drug designations.[5] The FDA granted the approval of Inrebic to Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation.[5]
Referencesedit
^"Summary Basis of Decision (SBD) for Inrebic". Health Canada. 23 October 2014. Retrieved 29 May 2022.
^ abc"Inrebic- fedratinib hydrochloride capsule". DailyMed. Retrieved 3 March 2021.
^"Inrebic Product information". Union Register of medicinal products. Retrieved 3 March 2023.
^ abcdef"FDA approves treatment for patients with rare bone marrow disorder". U.S. Food and Drug Administration (FDA) (Press release). 16 August 2019. from the original on 21 November 2019. Retrieved 16 August 2019. This article incorporates text from this source, which is in the public domain.
^ ab"Drug Trials Snapshots: Inrebic". U.S. Food and Drug Administration (FDA). 30 August 2019. from the original on 21 November 2019. Retrieved 20 November 2019. This article incorporates text from this source, which is in the public domain.
^Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM, Silverman MH, Gilliland DG, Shorr J, Tefferi A (March 2011). "Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis". Journal of Clinical Oncology. 29 (7): 789–796. doi:10.1200/JCO.2010.32.8021. PMC4979099. PMID 21220608.
^Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G, Finke C, Mak CC, Mesa R, Zhu H, Soll R, Gilliland DG, Tefferi A (August 2007). "TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations". Leukemia. 21 (8): 1658–1668. doi:10.1038/sj.leu.2404750. PMID 17541402. S2CID 22723501.
^. Celgene (Press release). 7 January 2018. Archived from the original on 31 October 2021. Retrieved 18 January 2018.
External linksedit
Clinical trial number NCT01437787 for "Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis (JAKARTA)" at ClinicalTrials.gov
fedratinib, sold, under, brand, name, inrebic, anti, cancer, medication, used, treat, myeloproliferative, diseases, including, myelofibrosis, used, form, fedratinib, hydrochloride, capsules, that, taken, mouth, semi, selective, inhibitor, janus, kinase, approv. Fedratinib sold under the brand name Inrebic is an anti cancer medication used to treat myeloproliferative diseases including myelofibrosis 5 It is used in the form of fedratinib hydrochloride capsules that are taken by mouth It is a semi selective inhibitor of Janus kinase 2 JAK 2 5 6 It was approved by the FDA on 16 August 2019 5 FedratinibClinical dataTrade namesInrebicOther namesSAR302503 TG101348AHFS Drugs comMonographLicense dataEU EMA by INN US DailyMed InrebicRoutes ofadministrationBy mouthDrug classAntineoplastic agentATC codeL01EJ02 WHO Legal statusLegal statusCA only 1 US only 2 EU Rx only 3 4 IdentifiersIUPAC name N tert Butyl 3 5 methyl 2 4 2 pyrrolidin 1 yl ethoxy phenylamino pyrimidin 4 ylamino benzenesulfonamideCAS Number936091 26 8 YPubChem CID16722836DrugBankDB12500ChemSpider17626393UNII6L1XP550I6KEGGD10630ChEBICHEBI 91408ChEMBLChEMBL1287853CompTox Dashboard EPA DTXSID90239483Chemical and physical dataFormulaC 27H 36N 6O 3SMolar mass524 68 g mol 13D model JSmol Interactive imageDensity1 247 0 06 g cm3SMILES CC1 CN C N C1NC2 CC CC C2 S O O NC C C C NC3 CC C C C3 OCCN4CCCC4InChI 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 Key JOOXLOJCABQBSG UHFFFAOYSA N N Y what is this Myelofibrosis is a myeloid cancer associated with anemia splenomegaly and constitutional symptoms Patients with myelofibrosis frequently harbor mutations which activate the JAK STAT signaling pathway and which are sensitive to fedratinib Phase I trial results focused on safety and efficacy of fedratinib in patients with high or intermediate risk primary or post polycythemia vera essential thrombocythemia myelofibrosis have been published in 2011 7 Contents 1 Medical uses 2 Pharmacology 2 1 Mechanism of action 3 History 4 References 5 External linksMedical uses editIn the United States fedratinib is indicated for the treatment of adults with intermediate 2 or high risk primary or secondary following polycythemia vera or essential thrombocythemia myelofibrosis 2 In the European Union fedratinib is indicated for the treatment of disease related splenomegaly or symptoms in adults with primary myelofibrosis following polycythaemia vera or essential thrombocythaemia who are Janus kinase JAK inhibitor naive or have been treated with ruxolitinib 3 Pharmacology editMechanism of action edit Fedratinib acts as a competitive inhibitor of protein kinase JAK 2 with IC50 6 nM related kinases FLT3 and RET are also sensitive with IC50 25 nM and IC50 17 nM respectively Significantly less activity was observed against other tyrosine kinases including JAK3 IC50 169 nM 8 In treated cells the inhibitor blocks downstream cellular signalling JAK STAT leading to suppression of proliferation and induction of apoptosis History editFedratinib was originally discovered at TargeGen In 2010 Sanofi Aventis acquired TargeGen and continued development of fedratinib until 2013 In 2016 Impact Biomedicines acquired the rights to fedratinib from Sanofi and continued its development for the treatment of myelofibrosis and polycythemia vera In January 2018 the drug s rights were transferred to Celgene with their purchase of Impact Biomedicines 9 Fedratinib was approved for medical use in the United States in August 2019 2 5 6 The U S Food and Drug Administration FDA granted the application for fedratinib priority review and orphan drug designations 5 The FDA granted the approval of Inrebic to Impact Biomedicines Inc a wholly owned subsidiary of Celgene Corporation 5 References edit Summary Basis of Decision SBD for Inrebic Health Canada 23 October 2014 Retrieved 29 May 2022 a b c Inrebic fedratinib hydrochloride capsule DailyMed Retrieved 3 March 2021 a b Inrebic EPAR European Medicines Agency EMA 9 December 2020 Retrieved 3 March 2021 Text was copied from this source which is c European Medicines Agency Reproduction is authorized provided the source is acknowledged Inrebic Product information Union Register of medicinal products Retrieved 3 March 2023 a b c d e f FDA approves treatment for patients with rare bone marrow disorder U S Food and Drug Administration FDA Press release 16 August 2019 Archived from the original on 21 November 2019 Retrieved 16 August 2019 nbsp This article incorporates text from this source which is in the public domain a b Drug Trials Snapshots Inrebic U S Food and Drug Administration FDA 30 August 2019 Archived from the original on 21 November 2019 Retrieved 20 November 2019 nbsp This article incorporates text from this source which is in the public domain Pardanani A Gotlib JR Jamieson C Cortes JE Talpaz M Stone RM Silverman MH Gilliland DG Shorr J Tefferi A March 2011 Safety and efficacy of TG101348 a selective JAK2 inhibitor in myelofibrosis Journal of Clinical Oncology 29 7 789 796 doi 10 1200 JCO 2010 32 8021 PMC 4979099 PMID 21220608 Pardanani A Hood J Lasho T Levine RL Martin MB Noronha G Finke C Mak CC Mesa R Zhu H Soll R Gilliland DG Tefferi A August 2007 TG101209 a small molecule JAK2 selective kinase inhibitor potently inhibits myeloproliferative disorder associated JAK2V617F and MPLW515L K mutations Leukemia 21 8 1658 1668 doi 10 1038 sj leu 2404750 PMID 17541402 S2CID 22723501 Celgene to Acquire Impact Biomedicines Adding Fedratinib to Its Pipeline of Novel Therapies for Hematologic Malignancies Celgene Press release 7 January 2018 Archived from the original on 31 October 2021 Retrieved 18 January 2018 External links editClinical trial number NCT01437787 for Phase III Study of SAR302503 in Intermediate 2 and High Risk Patients With Myelofibrosis JAKARTA at ClinicalTrials gov Portal nbsp Medicine nbsp This antineoplastic or immunomodulatory drug article is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Fedratinib amp oldid 1213640044, wikipedia, wiki, book, books, library,
