Details of the Drug

General Information of Drug (ID: DM4ZBK6)

• Drug Name: Fedratinib
• Synonyms: TG101348

Indication

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Approved	[1]
Polycythemia vera	2A20.4	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 2:
  Molecular Weight (mw); 524.7
  Logarithm of the Partition Coefficient (xlogp); 4.8
  Rotatable Bond Count (rotbonds); 11
  Hydrogen Bond Donor Count (hbonddonor); 3
  Hydrogen Bond Acceptor Count (hbondacc); 9
• ADMET Property:
  Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 26.870 mgh/L [4]
  Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 1804 mcg/L [4]
  Absorption Tmax: The time to maximum plasma concentration (Tmax) is 1.75-3 h [4]
  Clearance: The clearance of drug is 13 L/h [4]
  Elimination: An oral dose of fedratinib is 77% eliminated in the feces with 23% as unchanged drug, and 5% is eliminated in the urine with 3% as unchanged drug [4]
  Half-life: The concentration or amount of drug in body reduced by one-half in 41 hours [4]
  Metabolism: The drug is metabolized via the CYP3A4, CYP2C19, and flavin-containing monooxygenase 3 [4]
  Vd: The volume of distribution (Vd) of drug is 1770 L [4]
• Chemical Identifiers:
  Formula: C27H36N6O3S
  IUPAC Name: N-tert-butyl-3-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzenesulfonamide
  Canonical SMILES: CC1=CN=C(N=C1NC2=CC(=CC=C2)S(=O)(=O)NC(C)(C)C)NC3=CC=C(C=C3)OCCN4CCCC4
  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)
  InChIKey: JOOXLOJCABQBSG-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 16722836
  ChEBI ID: CHEBI:91408
  CAS Number: 936091-26-8
  DrugBank ID: DB12500
  TTD ID: D0G8BM
  ACDINA ID: D01069
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Inhibitor	[1]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Gene/Protein Processing	[5]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Gene/Protein Processing	[5]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Gene/Protein Processing	[5]
Suppressor of cytokine signaling 3 (SOCS3)	OTY183WJ	SOCS3_HUMAN	Gene/Protein Processing	[6]
Vascular endothelial growth factor A, long form	OTIM9MZ3	VEGFA_HUMAN	Gene/Protein Processing	[5]

Molecular Expression Atlas of This Drug

• The Studied Disease: Myelofibrosis
• ICD Disease Classification: 2A20.2

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Janus kinase 2 (JAK-2)	DTT	JAK2	2.46E-01	-0.41	-0.6

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Fedratinib (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Fedratinib and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[7]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Fedratinib caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[8]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Fedratinib and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[8]
Tazemetostat	DMWP1BH	Major	Decreased metabolism of Fedratinib caused by Tazemetostat mediated inhibition of CYP450 enzyme.	Follicular lymphoma [2A80]	[9]
Ripretinib	DM958QB	Moderate	Decreased metabolism of Fedratinib caused by Ripretinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[7]
Avapritinib	DMK2GZX	Major	Decreased metabolism of Fedratinib caused by Avapritinib mediated inhibition of CYP450 enzyme.	Gastrointestinal stromal tumour [2B5B]	[8]
Berotralstat	DMWA2DZ	Minor	Decreased metabolism of Fedratinib caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[8]
Pemigatinib	DM819JF	Major	Decreased metabolism of Fedratinib caused by Pemigatinib mediated inhibition of CYP450 enzyme.	Liver cancer [2C12]	[8]
Lurbinectedin	DMEFRTZ	Major	Decreased metabolism of Fedratinib caused by Lurbinectedin mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[10]
Pralsetinib	DMWU0I2	Moderate	Decreased metabolism of Fedratinib caused by Pralsetinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[11]
Selpercatinib	DMZR15V	Major	Decreased metabolism of Fedratinib caused by Selpercatinib mediated inhibition of CYP450 enzyme.	Lung cancer [2C25]	[8]
Ubrogepant	DM749I3	Moderate	Decreased metabolism of Fedratinib caused by Ubrogepant mediated inhibition of CYP450 enzyme.	Migraine [8A80]	[12]
Darolutamide	DMV7YFT	Minor	Decreased metabolism of Fedratinib caused by Darolutamide mediated inhibition of CYP450 enzyme.	Prostate cancer [2C82]	[13]
Upadacitinib	DM32B5U	Moderate	Decreased metabolism of Fedratinib caused by Upadacitinib mediated inhibition of CYP450 enzyme.	Rheumatoid arthritis [FA20]	[14]
Voxelotor	DMCS6M5	Moderate	Decreased metabolism of Fedratinib caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[8]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Fedratinib caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[7]
Fluticasone	DMGCSVF	Moderate	Decreased metabolism of Fedratinib caused by Fluticasone mediated inhibition of CYP450 enzyme.	Vasomotor/allergic rhinitis [CA08]	[7]

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Sodium stearyl fumarate	E00545	23665634	lubricant
Gelatin	E00630	Not Available	Other agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Haematite red	E00236	14833	Colorant

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Fedratinib 100 mg capsule	100 mg	Capsule	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

• [1] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [2] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 212327
• [3] TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect. 2020 Mar 11. pii: S1684-1182(20)30065-7.
• [4] FDA Approved Drug Products: Fedratinib Oral Capsules
• [5] Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors. Eur J Pharmacol. 2015 Oct 15;765:188-97. doi: 10.1016/j.ejphar.2015.08.037. Epub 2015 Aug 20.
• [6] The antimicrobial drug pyrimethamine inhibits STAT3 transcriptional activity by targeting the enzyme dihydrofolate reductase. J Biol Chem. 2022 Feb;298(2):101531. doi: 10.1016/j.jbc.2021.101531. Epub 2021 Dec 23.
• [7] Cerner Multum, Inc. "Australian Product Information.".
• [8] Cerner Multum, Inc. "UK Summary of Product Characteristics.".
• [9] Product Information. Tazverik (tazemetostat). Epizyme, Inc, Cambridge, MA.
• [10] Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
• [11] Product Information. Gavreto (pralsetinib). Blueprint Medicines Corporation, Cambridge, MA.
• [12] Product Information. Ubrelvy (ubrogepant). Allergan Inc, Irvine, CA.
• [13] Product Information. Nubeqa (darolutamide). Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
• [14] Product Information. Rinvoq (upadacitinib). AbbVie US LLC, North Chicago, IL.