Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0059)
Name
Itraconazole
Synonyms
itraconazole; Sporanox; 84625-61-6; Oriconazole; Itraconazol; Sporonox; Itrizole (TN); Itraconazolum; Sporal; Itrizole; Sporanox (TN); ITCZ; Orungal; Itraconazol [Spanish]; Fungitraxx; Itraconazolo; 873066-43-4; Candistat; Canditral; Hyphanox; Itralek; Sempera; Sporamelt; Traconal; Triasporin; Itrac; Cladosal 100; C35H38Cl2N8O4; Spherazole CR; Spherazole IR; DTXSID3023180; Itraconazole (Sporanox); R-51211; NSC-759239; Itraconazolum [Latin]; cis-Itraconazole; 304NUG5GF4; CHEBI:6076; DTXCID903180; 2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one; ITZ; R51211; SUBA Itraconazole; ITRACONAZOLE (EMA EPAR: VETERINARY); SUBA-ITRACONAZOLE COMPONENT ITRACONAZOLE; UNII-304NUG5GF4; ITRACONAZOLE COMPONENT OF SUBA-ITRACONAZOLE; ITRACONAZOLE (MART.); ITRACONAZOLE [MART.]; 3H-1,2,4-Triazol-3-one, 4-(4-(4-(4-((2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl)methoxy)phenyl)-1-piperazinyl)phenyl)-2,4-dihydro-2-(1-methylpropyl)-; Onmel; ITRACONAZOLE (USP-RS); ITRACONAZOLE [USP-RS]; HSDB 7839; ITRACONAZOLE (EP IMPURITY); ITRACONAZOLE [EP IMPURITY]; ITRACONAZOLE (EP MONOGRAPH); ITRACONAZOLE [EP MONOGRAPH]; R 51211; EINECS 283-347-2; ITRACONAZOLE (USP MONOGRAPH); ITRACONAZOLE [USP MONOGRAPH]; Itraconazolum (Latin); BRN 6042047; 2-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-2,4-dihydro-3H-1,2,4-triazol-3-one; 4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-sec-butyl-1,2,4-triazol-3-one; CAS-84625-61-6; R 51,211; Intraconazole; Lozanoc; Sporanos; Triasporn; NSC 759239; Sporanox(TM); NCGC00018268-03; 4-(4-{4-[4-({[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl}oxy)phenyl]piperazin-1-yl}phenyl)-2-(1-methylpropyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; DRG-0044; TOLSURA; Itraconazole & Nyotran; MFCD00941396; ITRACONAZOLE [MI]; ITRACONAZOLE [INN]; ITRACONAZOLE [JAN]; ITRACONAZOLE [INCI]; ITRACONAZOLE [USAN]; Itraconazole (JP17/USP); ITRACONAZOLE [VANDF]; SCHEMBL23934; 84604-65-9; MLS006011958; CHEMBL22587; ITRACONAZOLE [WHO-DD]; AMY922; GTPL11426; ITRACONAZOLE [GREEN BOOK]; J02AC02; ITRACONAZOLE [ORANGE BOOK]; Pharmakon1600-01505756; 4-(4-(4-(4-((2-((1H-1,2,4-Triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-2-(sec-butyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; Tox21_110854; AC-542; BDBM50127138; NSC759239; s2476; 3H-1,2,4-Triazol-3-one, 4-; AKOS015842738; AKOS015961385; Tox21_110854_1; CCG-270391; DB01167; KS-1268; NCGC00274068-01; NCGC00274068-02; NCGC00274068-07; 1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one; 4-(4-(4-(4-(((2R,4S)-2-((1H-1,2,4-triazol-1-yl)methyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)phenyl)-2-(sec-butyl)-2,4-dihydro-3H-1,2,4-triazol-3-one; HY-17514; SMR001827898; Itraconazole & Nyotran(Liposomal Nystatin); SBI-0206914.P001; SW219756-1; Itraconazole 2.0 mg/ml in Dimethyl Sulfoxide; D00350; EN300-122640; AB01274818-01; AB01274818_02; AB01274818_03; A933954; Q411229; BRD-A23067620-001-01-7; Z1544404944; (+/-)-1-SEC-BUTYL-4-(P-(4-(P-(((2R*,4S*)-2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)-1-PIPERAZINYL)PHENYL)-.DELTA.(SUP 2)-1,2,4-TRIAZOLIN-5-ONE; 1-(butan-2-yl)-4-{4-[4-(4-{[(2R,4S)-2-(2,4-dichlorophenyl)-2-[(1H-1,2,4-triazol-1-yl)methyl]-1,3-dioxolan-4-yl]methoxy}phenyl)piperazin-1-yl]phenyl}-4,5-dihydro-1H-1,2,4-triazol-5-one; 3H-1,2,4-Triazol-3-one, 4-[4-[4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-1-pipera-zinyl]phenyl]-2,4-dihydro-2-(1-methylpropyl)

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Structure
Formula
C35H38Cl2N8O4
IUPAC Name
2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one
Canonical SMILES
CCC(C)N1C(=O)N(C=N1)C2=CC=C(C=C2)N3CCN(CC3)C4=CC=C(C=C4)OCC5COC(O5)(CN6C=NC=N6)C7=C(C=C(C=C7)Cl)Cl
InChI
InChI=1S/C35H38Cl2N8O4/c1-3-25(2)45-34(46)44(24-40-45)29-7-5-27(6-8-29)41-14-16-42(17-15-41)28-9-11-30(12-10-28)47-19-31-20-48-35(49-31,21-43-23-38-22-39-43)32-13-4-26(36)18-33(32)37/h4-13,18,22-25,31H,3,14-17,19-21H2,1-2H3/t25?,31-,35-/m0/s1
InChIKey
VHVPQPYKVGDNFY-ZPGVKDDISA-N
PubChem CID
55283
Full List of Ferroptosis Target Related to This Drug
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
 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 Driver
Responsed Disease Squamous cell carcinoma of skin ICD-11: 2C31
 Disease Info 
Responsed Regulator Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model A-431 cells Skin squamous cell carcinoma Homo sapiens CVCL_0037
COLO 16 cells Skin squamous cell carcinoma Homo sapiens CVCL_D607
In Vivo Model
Female BALB/c nude mice (6weeks old and 18-22 g weight) were purchased from the Model Animal Research Center of Nanjing University. A431 cells (5 x 106) in cold DMEM (50 ul) were mixed with Matrigel (50 ul) and injected into mice subcutaneously. After 6 days, the tumor volume was measured and the mice were assigned to three groups. Mice were treated with either normal saline or itraconazole (40 mg/kg oral twice daily; 80 mg/kg oral twice daily).

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Response regulation Itraconazole inhibited the cell proliferation, induced apoptosis and blocked cell cycle of Cutaneous squamous cell carcinoma cells. And 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were significantly upregulated in A431 cells treated with itraconazole. Itraconazole may induce ferroptosis via HMGCS1/ACSL4 axis in A431 cells.
References
Ref 1 Itraconazole Inhibits the Growth of Cutaneous Squamous Cell Carcinoma by Targeting HMGCS1/ACSL4 Axis. Front Pharmacol. 2022 Feb 15;13:828983. doi: 10.3389/fphar.2022.828983. eCollection 2022.