Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0053)
Name
Artemether
Synonyms
Artemether; 71963-77-4; beta-Artemether; Dihydroartemisinin methyl ether; Artemetherum; Artenam; Artemisininelactol methyl ether; Methyl-dihydroartemisinine; Artemetero; Artemos; Artesaph; Falcidol; Gvither; Malartem; Paluther; beta-Dihydroartemisinin methyl ether; SM 224; Artemetheri; Dihydroqinghaosu methyl ether; CHEBI:195280; Larither; DTXSID7040651; CPD000469218; (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane; .beta.-Artemether; SM-224; Artemetero [INN-Spanish]; Artemetherum [INN-Latin]; methoxy(trimethyl)[?]; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-Decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-Decahydro-10-methoxy-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin; 10-methoxy-1,5,9-trimethyl-(1R,4S,5R,8S,9R,10S,12R,13R)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane; Dihydroquinghaosu methyl ether; HSDB 7456; C7D6T3H22J; NSC 665970; UNII-C7D6T3H22J; Artimist; Qinghao; SM224; beta artemether; Artemether [USAN:INN:BAN]; CGP 56696; NSC665970; NSC-665970; NSC-759820; NCGC00164591-01; (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane; Dihydroartemisinin impurity g; MLS001424249; Artemether (JAN/USAN/INN); CHEMBL566534; GTPL9955; SCHEMBL1650501; Artemether, >=98% (HPLC); DTXCID30819889; SXYIRMFQILZOAM-HVNFFKDJSA-N; HMS2052L09; HMS2232J21; 3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin, decahydro-10-methoxy-3,6,9-trimethyl-, (3R,5aS,6R,8aS,9R,10S,12R,12aR)-; AMY25769; HY-N0402; Tox21_112217; BDBM50248200; AKOS026750084; CCG-101180; DB06697; NC00430; 3,12-Epoxy-12H-pyrano(4,3-j)-1,2-benzodioxepin, decahydro-10-methoxy-3,6,9-trimethyl-, (3-alpha,5a-beta,6-beta,8a-beta,9-alpha,12-beta,12aR)-, (+)-; Artemether 100 microg/mL in Acetonitrile; SMR000469218; CAS-71963-77-4; D02483; EN300-122380; AB00698368-05; AB00698368_06; Q416199; 2-Chloro-3,5-dimethyl-4-methoxypyridinehydrochloride; Z1541759910; Artemether, United States Pharmacopeia (USP) Reference Standard; (1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0;{4,13}.0;{8,13}]hexadecane; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano[4,3-j][1,2]benzodioxepine; (3R,5aS,6R,8aS,9R,10S,12R,12aR)-10-methoxy-3,6,9-trimethyldecahydro-3H-3,12-epoxy[1,2]dioxepino[4,3-i]isochromene; (3r,5as,6r,8as,9r,10s,12r,12ar)-decahydro-10methoxy-3,6,9-trimethyl-3,12-epoxy-12h-pyrano[4,3-j]-1,2benzodioxepin; D8Z

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Structure
Formula
C16H26O5
IUPAC Name
(1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
Canonical SMILES
CC1CCC2C(C(OC3C24C1CCC(O3)(OO4)C)OC)C
InChI
InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1
InChIKey
SXYIRMFQILZOAM-HVNFFKDJSA-N
PubChem CID
68911
Full List of Ferroptosis Target Related to This Drug
Iron-responsive element-binding protein 2 (IREB2)
 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 Liver fibrosis ICD-11: DB93
 Disease Info 
Pathway Response Ferroptosis hsa04216
Ubiquitin mediated proteolysis hsa04120
Cell Process Cell ferroptosis
In Vitro Model hHSCs (Human hepatic stellate cells)
HSC-T6 cells Normal Rattus norvegicus CVCL_0315
LO #2 cells Amelanotic melanoma Homo sapiens CVCL_C7SD
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
In Vivo Model
The animal experiment scheme was approved by the institution of Nanjing University ofChinese Medicine (Nanjing, China) and the local animal protection and utilization committee. After the last administration, diet was prohibited, but drinking water was not restricted. 24 h later, the mice were weighed and taken blood.

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Response regulation ART (artemether) could lead to the accumulation of IRP2 a in hepatic stellate cell by inhibiting the ubiquitination of it, thus inducing the increase of iron in HSC (hepatic stellate cell), which could product a large number of ROS (reactive oxide species), resulting the occurrence of ferroptosis in cells. The findings provided an experimental basis for ART to become a drug for the treatment of liver fibrosis.
References
Ref 1 Iron regulatory protein 2 is required for artemether -mediated anti-hepatic fibrosis through ferroptosis pathway. Free Radic Biol Med. 2020 Nov 20;160:845-859. doi: 10.1016/j.freeradbiomed.2020.09.008. Epub 2020 Sep 15.