Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0254)
Name
Icariside II
Synonyms
Baohuoside I; 113558-15-9; Icariside II; Icarlin II; BAOHUOSIDEI; CHEBI:82619; 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one; CHEMBL560116; 3,5,7-Trihydroxy-4'-methoxyl-8-prenylflavone-3-O-rhamnopyranoside; Icariin-II;Icariside-II; Baohuoside-I; Icariside-II; Icariin-II; AMY496; SCHEMBL4229321; GTPL10686; DTXSID40150457; 2h44; EX-A6795; HY-N0011; BDBM50503751; AKOS037514560; CS-3673; 4H-1-Benzopyran-4-one, 3-((6-deoxy-alpha-L-mannopyranosyl)oxy)-5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methyl-2-butenyl)-; AC-33977; AS-75062; anhydroicaritin-3-O-alpha-L-rhamnopyranoside; Baohuoside I; Anhydroicaritin; Icariside II; A894345; Q-100071; Q27156136; 3,5,7-trihydroxy-4'-methoxy-8-prenylflavone-3-O-rhamnopyranoside; 3,5,7-trihydroxy-4'-methoxy-8-prenylflavone-3-O-alpha-L-rhamnopyranoside; 3,5,7-Trihydroxy-4'-methoxyl-8-prenylflavone-3-O-rhamnopyranoside; 4H-1-Benzopyran-4-one, 3-((6-deoxy-alpha-L-mannopyranosyl)oxy)-5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methyl-2-butenyl)-; 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3-yl 6-deoxy-alpha-L-mannopyranosideohuside I; Icariin II; Icariside II; 4H-1-Benzopyran-4-one, 3-[(6-deoxy-alpha-L-mannopyranosyl)oxy]-5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methyl-2-buten-1-yl)-; 5,7-Dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-3-(((2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-4H-chromen-4-one; 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-3-{[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}-4H-chromen-4-one; 5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3-yl 6-deoxy-alpha-L-mannopyranoside

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C27H30O10
IUPAC Name
5,7-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one
Canonical SMILES
CC1C(C(C(C(O1)OC2=C(OC3=C(C(=CC(=C3C2=O)O)O)CC=C(C)C)C4=CC=C(C=C4)OC)O)O)O
InChI
InChI=1S/C27H30O10/c1-12(2)5-10-16-17(28)11-18(29)19-21(31)26(37-27-23(33)22(32)20(30)13(3)35-27)24(36-25(16)19)14-6-8-15(34-4)9-7-14/h5-9,11,13,20,22-23,27-30,32-33H,10H2,1-4H3/t13-,20-,22+,23+,27-/m0/s1
InChIKey
NGMYNFJANBHLKA-LVKFHIPRSA-N
PubChem CID
5488822
TTD Drug ID
D06TLQ
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 Hereditary Leiomyomatosis ICD-11: 2C90
 Disease Info 
Responsed Regulator hsa-miR-324-3p (miRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model ACHN cells Papillary renal cell carcinoma Homo sapiens CVCL_1067
A-498 cells Renal cell carcinoma Homo sapiens CVCL_1056
786-O cells Renal cell carcinoma Homo sapiens CVCL_1051
Caki-1 cells Clear cell renal cell carcinoma Homo sapiens CVCL_0234
HEK-293T cells Normal Homo sapiens CVCL_0063
In Vivo Model
A total of 30 male BALB/c nude mice (4-6 weeks old; 18-23 g) were randomized into four groups (7-8 mice per group): i) control group; ii) treated with 15 mg/kg ICS II; iii) treated with 25 mg/kg ICS II; and, iv) treated with 35 mg/kg ICS II. ACHN and Caki-1 cells (1 x 107) were suspended in 50 ul MEM media mixed with 50 ul Matrigel (BD Biosciences) and injected subcutaneously into the right flank of mice with 1.5%pentobarbital sodium (60 mg/kg body weight; intraperitoneal injection) under anesthesia. Weight lossof more than 20% was considered a humane endpoint.

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Response regulation Icariside II (ICS II) treatment triggered ferroptosis in renal cell carcinoma (RCC) cells by downregulating GPX4 in a p53-independent manner. Furthermore, ICS II treatment resulted in upregulation of miR-324-3p, which negatively regulated the expression of GPX4.
References
Ref 1 Icariside II induces ferroptosis in renal cell carcinoma cells by regulating the miR-324-3p/GPX4 axis. Phytomedicine. 2022 Jul 20;102:154182. doi: 10.1016/j.phymed.2022.154182. Epub 2022 May 17.