Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0288)
Name
Tubastatin A
Synonyms
Tubastatin A; 1252003-15-8; Tubastatin-A; Tubastatin A BASE; Tubastatin A (free base); 2XTSOX1NF8; N-hydroxy-4-((2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)methyl)benzamide; Tubastatin A(free base); UNII-2XTSOX1NF8; N-hydroxy-4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzamide; Tubastatin A (trifluoroacetate); CHEMBL2018302; 1252003-15-8 (free base); Benzamide, N-hydroxy-4-((1,2,3,4-tetrahydro-2-methyl-5H-pyrido(4,3-b)indol-5-yl)methyl)-; N-Hydroxy-4-((1,2,3,4-tetrahydro-2-methyl-5H-pyrido(4,3-b)indol-5-yl)methyl)benzamide; Tubastatin A Trifluoroacetate; 4-[(2-methyl-3,4-dihydro-1~{H}-pyrido[4,3-b]indol-5-yl)methyl]-~{N}-oxidanyl-benzamide; TubaststinA HCl; N-Hydroxy-4-((2-methyl-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)methyl)benzamide; N-hydroxy-4-[(2-methyl-1,2,3,4-tetrahydro-5H-pyrido[4,3-b]indol-5-yl)methyl]benzamide; Benzamide, N-hydroxy-4-[(1,2,3,4-tetrahydro-2-methyl-5H-pyrido[4,3-b]indol-5-yl)methyl]-; N9W; MLS006011088; GTPL9702; SCHEMBL1057119; CHEBI:94186; EX-A685; GOVYBPLHWIEHEJ-UHFFFAOYSA-N; DTXSID701318079; HMS3656P20; HMS3744E15; BCP09011; CAC00315; BDBM50380399; HY-13271A; MFCD18071463; s8049; AKOS027422742; CCG-267860; CS-5376; SB19289; NCGC00263606-03; NCGC00263606-15; AS-16945; SMR004702876; FT-0700144; SW219287-2; EC-000.2473; US8748451, 6; J-690100; BRD-K00627859-001-01-5; Q27165946; 4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzenecarbohydroxamic acid; N-hydroxy-4-(2-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-ylmethyl)benzamide; 1-(4-{[2-(1H-Indazol-4-yl)-4-(4-morpholinyl)thieno[3,2-d]pyrimidin-6-yl]methyl}-1-piperazinyl)-6-methyl-5-heptene-1,4-dione

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Structure
Formula
C20H21N3O2
IUPAC Name
N-hydroxy-4-[(2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5-yl)methyl]benzamide
Canonical SMILES
CN1CCC2=C(C1)C3=CC=CC=C3N2CC4=CC=C(C=C4)C(=O)NO
InChI
InChI=1S/C20H21N3O2/c1-22-11-10-19-17(13-22)16-4-2-3-5-18(16)23(19)12-14-6-8-15(9-7-14)20(24)21-25/h2-9,25H,10-13H2,1H3,(H,21,24)
InChIKey
GOVYBPLHWIEHEJ-UHFFFAOYSA-N
PubChem CID
49850262
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 Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
In Vivo Model
Female 5-week-old athymic nude mice were obtained from Sun Yat-sen University. All mice were kept under specific-pathogen free conditions in the animal facility of Sun Yat-sen University Cancer Centre. Cancer cells were suspended and counted in 1 x DMEM, and 2 x 106 MDA-MB-231 cells were injected into mice subcutaneously. When the tumours reached 50-100 mm3, the mice were randomly assigned to different treatment groups. Tumours were irradiated with a JL Shepherd Mark I-68A irradiator at a dose of 10 Gy. Tub was dissolved in solvent containing 1% DMSO, 30% polyethylene glycol, 1% Tween 80 and 68% H2O and then subcutaneously administered to mice at a dose of 2.5 mg/kg once a day. Lipro-1 diluted in PBS was intraperitoneally injected daily at a dose of 10 mg/kg. Tub or Lipro-1 was administered three times before irradiation followed by continued daily administration until the endpoint, as indicated in the corresponding figures.

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Response regulation Tubastatin A (Tub) as a novel GPX4 inhibitor that induced ferroptosis through large-scale drug screening. We showed that IR-mediated GPX4 expression restrained ferroptosis to drive radioresistance in breast cancer.
References
Ref 1 Tubastatin A potently inhibits GPX4 activity to potentiate cancer radiotherapy through boosting ferroptosis. Redox Biol. 2023 Jun;62:102677. doi: 10.1016/j.redox.2023.102677. Epub 2023 Mar 17.