Drug Information

Drug (ID: DG01239) and It's Reported Resistant Information

• Name: Fedratinib
• Synonyms: Fedratinib; 936091-26-8; Tg-101348; TG101348; SAR302503; N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide; TG 101348; SAR-302503; Fedratinib (SAR302503, TG101348); SAR 302503; UNII-6L1XP550I6; TG101348 (SAR302503); N-(1,1-Dimethylethyl)-3-[[5-methyl-2-[[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]amino]-4-pyrimidinyl]amino]benzenesulfonamide; CHEMBL1287853; C27H36N6O3S; 6L1XP550I6; 936091-26-8 (free base); N-tert-butyl-3-(5-methyl-2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide; N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzenesulfonamide; Inrebic; Fedratinib [USAN:INN]; 2TA; Fedratinib (USAN/INN); Fedratinib TG101348; TG101348(Fedratinib); Fedratinib (TG101348); MLS006011155; SCHEMBL263741; GTPL5716; CHEBI:91408; AOB2041; DTXSID90239483; EX-A170; SYN1104; HMS3295I03; HMS3656L19; HMS3744G17; HMS3868L03; BCP02300; BDBM50332294; MFCD12922515; NSC767600; NSC800099; s2736; ZINC19862646; AKOS015842621; CCG-264990; CS-0052; DB12500; EX-5961; NSC-767600; NSC-800099; SB14604; NCGC00244252-01; NCGC00244252-07; AC-30260; AS-16248; Benzenesulfonamide, N-(1,1-dimethylethyl)-3-((5-methyl-2-((4-(2-(1-pyrrolidinyl)ethoxy)phenyl)amino)-4-pyrimidinyl)amino)-; DA-40258; HY-10409; N-Tert-butyl-3-(5-methyl-2-(4-(2-pyrrolidin-1-yl-ethoxy)-phenylamino)-pyrimidin-4-ylamino)-benzenesulfonamide; N-tert-butyl-3-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzenesulfonamide; SMR004702929; DB-079623; FT-0705969; FT-0763396; FT-0766818; SW218187-2; Y0268; A25534; D10630; F17372; SAR302503 (TG-101348); 091D268; J-523769; Q7670147; BRD-K12502280-001-01-5; 945381-69-1; Fedratinib; ; ; N-(1,1-Dimethylethyl)-3-[[5-methyl-2-[[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]amino]-4-pyrimidinyl]amino]-benzenesulfonamide; N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzene-1-sulfonamide
• Indication:
  In total 1 Indication(s)
  Myelofibrosis [ICD-11: 2A20]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Hematologic cancer [ICD-11: MG24]; [2]
• Target: Janus kinase 2 (JAK-2); JAK2_HUMAN; [1]
• Formula: C27H36N6O3S
• IsoSMILES: CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4
• 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)
• InChIKey: JOOXLOJCABQBSG-UHFFFAOYSA-N
• PubChem CID: 16722836
• ChEBI ID: CHEBI:91408
• TTD Drug ID: D0G8BM
• DrugBank ID: DB12500

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Chronic myeloid leukemia [ICD-11: 2A20]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [1]

• Molecule Alteration: Function; Inhibition
• Sensitive Disease: Primary myelofibrosis [ICD-11: 2A20.2]
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: In non-transplant candidates, conventional treatment for anemia includes androgens, prednisone, thalidomide, and danazol; for symptomatic splenomegaly, hydroxyurea and ruxolitinib; and for constitutional symptoms, ruxolitinib. Fedratinib, another JAK2 inhibitor, has now been FDA-approved for use in ruxolitinib failures.

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [3]

• Molecule Alteration: Missense mutation; p.V617F (c.1849G>T)
• Sensitive Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: HEL cells; Blood; Homo sapiens (Human); CVCL_0001
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: XTT assay
• Mechanism Description: The missense mutation p.V617F (c.1849G>T) in gene JAK2 cause the sensitivity of Fedratinib by aberration of the drug's therapeutic target

Hematologic cancer [ICD-11: 2B3Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Tyrosine-protein kinase JAK2 (JAK3) [2]

• Molecule Alteration: Missense mutation; p.R867Q (c.2600G>A)
• Resistant Disease: Hematologic Cancer [ICD-11: MG24.Y]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: WST-1 cell proliferation assay

References

• Ref 1: Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management .Am J Hematol. 2021 Jan;96(1):145-162. doi: 10.1002/ajh.26050. Epub 2020 Dec 2. 10.1002/ajh.26050
• Ref 2: Germ-line JAK2 mutations in the kinase domain are responsible for hereditary thrombocytosis and are resistant to JAK2 and HSP90 inhibitorsBlood. 2014 Feb 27;123(9):1372-83. doi: 10.1182/blood-2013-05-504555. Epub 2014 Jan 7.
• Ref 3: Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia veraCancer Cell. 2008 Apr;13(4):311-20. doi: 10.1016/j.ccr.2008.02.009.