fedratinib

a selective small-molecule inhibitor of JAK2

Also Known As:

Inrebic; N-tert-butyl-3-((5-methyl-2-((4-(2-pyrrolidin-1-ylethoxy)phenyl)amino)pyrimidin-4-yl)amino) benzenesulfonamide dihydrochloride monohydrate; N-tert-butyl-3-(5-methyl-2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino) pyrimidin-4-ylamino)benzenesulfonamide; SAR-302503; SAR-302503A; SAR302503; SAR302503A; TG-101348; TG101348; fedratinib dihydrochloride monohydrate; fedratinib hydrochloride; fedratinib hydrochloride monohydrate

Networked: 125 relevant articles (17 outcomes, 30 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Mesa, Ruben A: 12 articles (01/2022 - 09/2009)
2.	Verstovsek, Srdan: 11 articles (01/2022 - 01/2019)
3.	Krishna, Gopal: 10 articles (12/2021 - 10/2019)
4.	Talpaz, Moshe: 9 articles (01/2022 - 03/2011)
5.	Ogasawara, Ken: 9 articles (12/2021 - 10/2019)
6.	Palmisano, Maria: 9 articles (12/2021 - 10/2019)
7.	Harrison, Claire N: 8 articles (01/2022 - 07/2017)
8.	Kiladjian, Jean-Jacques: 8 articles (01/2022 - 07/2017)
9.	Vannucchi, Alessandro M: 8 articles (01/2022 - 08/2015)
10.	Passamonti, Francesco: 7 articles (01/2022 - 06/2011)

Related Diseases

1.	Primary Myelofibrosis (Myelosclerosis) 03/01/2011 - "TG101348 is well tolerated and produces significant reduction in disease burden and durable clinical benefit in patients with myelofibrosis." 01/01/2022 - "Safety and efficacy of fedratinib, a selective oral inhibitor of Janus kinase-2 (JAK2), in patients with myelofibrosis and low pretreatment platelet counts." 08/01/2015 - "Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial." 03/01/2011 - "Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis." 10/01/2021 - "Updated results of the placebo-controlled, phase III JAKARTA trial of fedratinib in patients with intermediate-2 or high-risk myelofibrosis."
2.	Splenomegaly 08/01/2015 - "Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF. " 01/01/2021 - "In mouse models of JAK2V617F-driven myeloproliferative disease, fedratinib blocked phosphorylation of STAT5, increased survival, and improved MF-associated disease features, including reduction of white blood cell counts, hematocrit, splenomegaly, and fibrosis. " 10/01/2021 - "Fedratinib, an oral Janus kinase-2 (JAK2) inhibitor, reduces splenomegaly and improves symptom burden in patients with myelofibrosis. " 06/01/2011 - "Treatment with ruxolitinib and TG101348 has shown clinically significant benefits, particularly in improvement of splenomegaly and constitutional symptoms in MF patients. " 01/01/2019 - "The approval of fedratinib was based on phase II trials and the phase III JAKARTA trial, in which the drug significantly reduced splenomegaly and symptom burden compared to placebo, including some patients previously treated with ruxolitinib. "
3.	Cytopenia 10/01/2022 - "We use fedratinib for symptomatic MF following ruxolitinib failure in patients without significant cytopenias; with practical strategies for monitoring and managing potential toxicity." 01/01/2020 - "Current frontline therapies for MF, include ruxolitinib and fedratinib, which can exacerbate cytopenias and thereby pose an impediment to effective treatment of the myelodepletive patient. " 06/01/2020 - "Fedratinib induces robust spleen responses, and pacritinib and momelotinib may have preferential activity in patients with severe cytopenias. " 04/01/2012 - "INCB018424, CYT387, SB1518, and TG101348 are among the most propitious JAK2 inhibitors under investigation, providing substantial improvement in constitutional symptoms, transfusion-dependent cytopenias, and reduction in spleen size. " 01/01/2023 - "However, early JAK inhibitors (ruxolitinib and fedratinib) are often associated with cytopenias, particularly thrombocytopenia and anemia, which limit their tolerability. "
4.	Anemia 01/01/2023 - "Using conventional criteria, the respective response rates for spleen and "transfusion-dependent anemia" were 47%, 32%, 83%, 62% and 51%, 30%, 10%, 44%, respectively, favoring momelotinib for anemia response (p = 0.02) and fedratinib for spleen response (p < 0.01). " 01/01/2022 - "Compared with other JAK inhibitors, the mechanism of action of fedratinib may explain its milder effect on anemia. " 12/01/2020 - "The most common adverse effects associated with fedratinib include anemia, gastrointestinal symptoms and elevation in liver transaminases. " 01/01/2019 - "The JAK2-selective inhibitor fedratinib has recently been resurrected, and there has been a resurgence of interest in the failed JAK1/2 inhibitor momelotinib, which possibly improves anemia. " 01/01/2019 - "The main side effects of fedratinib include anemia, gastrointestinal symptoms, and elevations in liver transaminases. "
5.	Polycythemia Vera 04/01/2008 - "Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera." 08/01/2015 - "Double-blind, randomized, placebo-controlled phase 3 study in 94 sites in 24 countries in which 289 adult patients (≥18 years of age) with intermediate-2 or high-risk primary MF, post-polycythemia vera MF, or post-essential thrombocythemia MF were randomly assigned between December 2011 and September 2012 to once-daily oral fedratinib, at a dose of 400 mg or 500 mg, or placebo, for at least 6 consecutive 4-week cycles. " 10/01/2019 - "The objectives of this analysis were to develop a population pharmacokinetic (PK) model to characterize fedratinib concentration-time profiles in patients with MF, polycythemia vera (PV) and essential thrombocythemia (ET) following oral fedratinib administration; and to investigate the effects of selected covariates on fedratinib PK parameters. " 08/01/2015 - "To evaluate the efficacy and safety of fedratinib therapy in patients with primary or secondary (post-polycythemia vera or post-essential thrombocythemia) MF. " 03/01/2011 - "In a multicenter phase I trial, oral TG101348 was administered once a day to patients with high- or intermediate-risk primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. "

Related Drugs and Biologics

1.	ruxolitinib
2.	N- (cyanomethyl)- 4- (2- ((4- (4- morpholinyl)phenyl)amino)- 4- pyrimidinyl)benzamide
3.	11- (2- pyrrolidin- 1- ylethoxy)- 14,19- dioxa- 5,7,26- triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa- 1(25),2(26),3,5,8,10,12(27),16,21,23- decaene
4.	Cytokines
5.	Janus Kinase Inhibitors
6.	Hydroxyurea (Hydrea)
7.	Imatinib Mesylate (Gleevec)
8.	fedratinib
9.	Janus Kinase 2
10.	Phosphotransferases (Kinase)

Related Therapies and Procedures

1.	Therapeutics