fedratinib   Click here for help

GtoPdb Ligand ID: 5716

Synonyms: Inrebic® | SAR302503 | TG-101348 | TG101348
Approved drug PDB Ligand
fedratinib is an approved drug (FDA (2019), EMA (2021))
Compound class: Synthetic organic
Comment: Fedratinib (TG‑101348) was initially reported as an orally active JAK2-FLT3 kinase inhibitor, with biological activity via JAK2 inhibition [6]. More recently, this compound has been discovered to function, in addition, as a BRD4 (bromodomain) inhibitor [2,4]. It is suggested that TG‑101348 be termed a dual kinase-bromodomain inhibitor. Fedratinib is been identified and officially approved as an alternative to the JAK1/2 inhibitor ruxolitinib for the treatment of primary and secondary myelofibrosis [1].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 3
Rotatable bonds 11
Topological polar surface area 116.86
Molecular weight 524.26
XLogP 4.26
No. Lipinski's rules broken 1
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Canonical SMILES Cc1cnc(nc1Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)Nc1ccc(cc1)OCCN1CCCC1
Isomeric SMILES Cc1cnc(nc1Nc1cccc(c1)S(=O)(=O)NC(C)(C)C)Nc1ccc(cc1)OCCN1CCCC1
InChI 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)
1. Bose P, Alfayez M, Verstovsek S. (2019)
New Concepts of Treatment for Patients with Myelofibrosis.
Curr Treat Options Oncol, 20 (1): 5. [PMID:30675650]
2. Ciceri P, Müller S, O'Mahony A, Fedorov O, Filippakopoulos P, Hunt JP, Lasater EA, Pallares G, Picaud S, Wells C et al.. (2014)
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.
Nat Chem Biol, 10 (4): 305-12. [PMID:24584101]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]
4. Ember SW, Zhu JY, Olesen SH, Martin MP, Becker A, Berndt N, Georg GI, Schönbrunn E. (2014)
Acetyl-lysine binding site of bromodomain-containing protein 4 (BRD4) interacts with diverse kinase inhibitors.
ACS Chem Biol, 9 (5): 1160-71. [PMID:24568369]
5. Malerich JP, Lam JS, Hart B, Fine RM, Klebansky B, Tanga MJ, D'Andrea A. (2010)
Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3.
Bioorg Med Chem Lett, 20 (24): 7454-7. [PMID:21106455]
6. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J et al.. (2008)
Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera.
Cancer Cell, 13 (4): 311-20. [PMID:18394554]
7. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem Biol, 17 (11): 1241-9. [PMID:21095574]