Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0194)
Name
Fedratinib
Synonyms
Fedratinib; 936091-26-8; Tg-101348; TG101348; SAR302503; SAR-302503; N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide; Inrebic; SAR 302503; TG 101348; Fedratinib (SAR302503, TG101348); N-(1,1-Dimethylethyl)-3-[[5-methyl-2-[[4-[2-(1-pyrrolidinyl)ethoxy]phenyl]amino]-4-pyrimidinyl]amino]benzenesulfonamide; TG101348 (SAR302503); CHEMBL1287853; 6L1XP550I6; 936091-26-8 (free base); N-tert-butyl-3-(5-methyl-2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide; Benzenesulfonamide, N-(1,1-dimethylethyl)-3-((5-methyl-2-((4-(2-(1-pyrrolidinyl)ethoxy)phenyl)amino)-4-pyrimidinyl)amino)-; 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; Fedratinib [USAN]; Fedratinib [USAN:INN]; UNII-6L1XP550I6; 2TA; FEDRATINIB [MI]; FEDRATINIB [INN]; Fedratinib (USAN/INN); TG101348(Fedratinib); FEDRATINIB [WHO-DD]; Fedratinib (TG101348); MLS006011155; N-tert-butyl-3-[[5-methyl-2-[4-(2-pyrrolidin-1-ylethoxy)anilino]pyrimidin-4-yl]amino]benzenesulfonamide; SCHEMBL263741; GTPL5716; CHEBI:91408; DTXSID90239483; EX-A170; HMS3295I03; HMS3656L19; HMS3744G17; HMS3868L03; BCP02300; BDBM50332294; MFCD12922515; NSC767600; NSC800099; s2736; AKOS015842621; CCG-264990; CS-0052; DB12500; EX-5961; NSC-767600; NSC-800099; SB14604; NCGC00244252-01; NCGC00244252-07; AC-30260; AS-16248; HY-10409; SMR004702929; FT-0705969; FT-0763396; FT-0766818; SW218187-2; A25534; D10630; F17372; J-523769; Q7670147; BRD-K12502280-001-01-5; Z2037280076; N-TERT-BUTYL-3-((5-METHYL-2-(4-(2-(PYRROLIDIN-1-YL)ETHOXY)ANILINO(PYRIMIDIN-4-YL)AMINO)BENZENESULFONAMIDE; N-tert-butyl-3-{[5-methyl-2-({4-[2-(pyrrolidin-1-yl)ethoxy]phenyl}amino)pyrimidin-4-yl]amino}benzene-1-sulfonamide; SAR302503, N-tert-butyl-3-(5-methyl-2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenylamino)pyrimidin-4-ylamino)benzenesulfonamide

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Structure
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
PubChem CID
16722836
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Acute kidney failure ICD-11: GB60
 Disease Info 
Responsed Regulator E3 ubiquitin-protein ligase TRIM21 (TRIM21) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Mice were fasted for 12 h and anesthetized (1% pentobarbital sodium, i.p.) before surgery. Bilateral renal pedicles were clamped for 30 min, then remove the arterial clamps. The sham groups were treated in the same way, except for the clamping of the renal pedicle. Blood samples were collected 24 h after reperfusion, mice were killed, and kidney were collected for follow-up experiments. Fedratinib (5 mg/kg body weight) was injected (i.p.) into mice 24 h once in advance before surgery.

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Response regulation A JAK2 inhibitor Fedratinib downregulated TRIM21 expression and reduced damage both in vivo and in vitro, which is correlated with the upregulation of GPX4. Our study showed that loss of TRIM21 could alleviate ferroptosis induced by I/R, revealed the mechanism of ubiquitination degradation of GPX4 by TRIM21 and suggested TRIM21 is a potential target for the treatment of acute kidney injury (AKI).
References
Ref 1 TRIM21 ubiquitylates GPX4 and promotes ferroptosis to aggravate ischemia/reperfusion-induced acute kidney injury. Life Sci. 2023 May 15;321:121608. doi: 10.1016/j.lfs.2023.121608. Epub 2023 Mar 21.