Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0166)
Name
Amentoflavone
Synonyms
Amentoflavone; 1617-53-4; Didemethyl-ginkgetin; 3',8''-Biapigenin; Amenthoflavone; Tridemethylsciadopitysin; MLS000574827; CHEBI:2631; 9I1VC79L77; MFCD00017470; NSC-295677; 8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one; 8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one; SMR000156235; 8-(5-(5,7-Dihydroxy-4-oxo-4H-chromen-2-yl)-2-hydroxyphenyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; 4H-1-Benzopyran-4-one, 8-(5-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2-hydroxyphenyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)-; 8-(5-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2-hydroxyphenyl)-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one; 8-[5-(5,7-dihydroxy-4-oxo-4H-chromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one; SR-01000721725; UNII-9I1VC79L77; 4H-1-Benzopyran-4-one, 8-[5-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-; NSC 295677; AMENTOFLAVONE [INCI]; BIDD:PXR0028; I3',II8-BIAPIGENIN; GINKGETIN, DIDEMETHYL-; SCHEMBL312563; MEGxp0_000924; med.21724, Compound 138; DTXSID20167225; Amentoflavone, analytical standard; YUSWMAULDXZHPY-UHFFFAOYSA-N; BDBM429466; HMS2228B12; HMS3343J17; HMS3885A08; -hydroxyphenyl)-5,7-dihydroxy-2-; BCP13255; BEA14006; HY-N0662; Amentoflavone, >=99.0% (HPLC); LMPK12040009; NSC295677; s3833; (4-hydroxyphenyl)-4H-chromen-4-one; AKOS015896819; CCG-269950; CS-4945; 3',8-Bi[4',5,7-trihydroxyflavone]; NCGC00247542-01; NCGC00247542-02; AC-34718; BS-15502; FT-0622262; A11476; A810291; 8-(5-(5,7-dihydroxy-4-oxo-4H-chromen-2-yl)-2; Q-100192; Q4742425; SR-01000721725-2; SR-01000721725-3; 4',5,7-Trihydroxyflavone(3'->8)-4',5,7-trihydroxyflavone; 3''',8-BIFLAVONE, 4',4''',5,5'',7,7''-HEXAHYDROXY; 4',4''',5,5'',7,7''-Hexahydroxy-3''',8-biflavone, 8CI; 4H-1-Benzopyran-4-one, 8-[5-(5,7-dihydroxy-4-oxo-4H-1-benzopyran-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl); 8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one;Amentoflavone; 8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one.

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C30H18O10
IUPAC Name
8-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
Canonical SMILES
C1=CC(=CC=C1C2=CC(=O)C3=C(O2)C(=C(C=C3O)O)C4=C(C=CC(=C4)C5=CC(=O)C6=C(C=C(C=C6O5)O)O)O)O
InChI
InChI=1S/C30H18O10/c31-15-4-1-13(2-5-15)24-12-23(38)29-21(36)10-20(35)27(30(29)40-24)17-7-14(3-6-18(17)33)25-11-22(37)28-19(34)8-16(32)9-26(28)39-25/h1-12,31-36H
InChIKey
YUSWMAULDXZHPY-UHFFFAOYSA-N
PubChem CID
5281600
TTD Drug ID
D06HRX
Full List of Ferroptosis Target Related to This Drug
Ferritin heavy chain (FTH1)
 Target Info 
In total 3 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Microtubule-associated proteins 1A/1B light chain 3B {ECO:0000305} (MAP1LC3B) Driver
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

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Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Autophagy protein 5 (ATG5) Driver
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

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Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Ubiquitin-like modifier-activating enzyme ATG7 (ATG7) Driver
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

    Click to Show/Hide
Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
Unspecific Target
In total 4 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator Cyclic AMP-dependent transcription factor ATF-2 (ATF2) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model GSE-1 (Human gastric mucosal epithelial cells)
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
In Vivo Model
The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks.

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Response regulation Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator hsa-miR-496 (miRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model GSE-1 (Human gastric mucosal epithelial cells)
AGS cells Gastric adenocarcinoma Homo sapiens CVCL_0139
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
In Vivo Model
The BALB/c nude mice (n = 15, 4-6 weeks old) were purchased from Charles River Labs and kept under controlled conditions. Then 1 x 106 AGS cells were inoculated subcutaneously into nude mice. When the tumor reached to 100 mm3, mice were randomly divided into three groups, the control group was intraperitoneally injected with saline, the AF group was intraperitoneally injected with AF at dosages of 80 mg/kg/day, and AF + anti-miR-496 group received intraperitoneal injection, followed by the administration of miR-496 antagonist via intra-tumor injection once a week for 4 weeks.

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Response regulation Amentoflavone suppressed the proliferation and induced ferroptotic cell death in gastric cancer cells via miR-496/ATF2 axis, indicating a novel therapeutic approach for GC patients.
Experiment 3 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Corpus uteri cancer ICD-11: 2C76
 Disease Info 
Responsed Regulator Serine/threonine-protein kinase mTOR (MTOR) Suppressor
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model hESCs (Human endometrial stromal cells)
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.
Experiment 4 Reporting the Ferroptosis-centered Drug Act on This Target [3]
Responsed Disease Corpus uteri cancer ICD-11: 2C76
 Disease Info 
Responsed Regulator 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1) Driver
 Regulator Info 
Pathway Response mTOR signaling pathway hsa04150
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model hESCs (Human endometrial stromal cells)
KLE cells Endometrial adenocarcinoma Homo sapiens CVCL_1329
Response regulation Amentoflavone inhibited the viability and proliferation of endometrial carcinoma cells (KLE) cells but promoted apoptosis and ferroptosis. The expressions of ROS and AMPK were increased, while mTOR expression was decreased in AF-treated KLE cells. NAC reversed the effects of AF on biological behaviors of KLE cells by inactivating ROS/AMPK/mTOR signaling.
Beclin-1 (BECN1)
 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 Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response mTOR signaling pathway hsa04150
Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
Cell proliferation
In Vitro Model U-251MG cells Astrocytoma Homo sapiens CVCL_0021
U-373MG cells Astrocytoma Homo sapiens CVCL_2219
In Vivo Model
1 x 107 U251 cells were subcutaneously injected into the right back of the four-week-old BALB/c nude mice. After the tumor grown to 100 mm3, mice were randomly divided into 3 groups: mice in control group receivedintraperitoneal injectionof saline, while mice in AF treatment group received intraperitoneal injection at dosages of 40 mg/kg/day or 80 mg/kg/day, respectively.

    Click to Show/Hide
Response regulation Amentoflavone (AF) triggered ferroptosis in autophagy-dependent manner. Furthermore, the expression of LC3B, Beclin1, ATG5, ATG7 were increased, and the expression of FTH were decreased by AF in a dose-dependent manner in vivo. AF has the potential to be considered as a novel treatment agent in glioma.
References
Ref 1 Amentoflavone suppresses cell proliferation and induces cell death through triggering autophagy-dependent ferroptosis in human glioma. Life Sci. 2020 Apr 15;247:117425. doi: 10.1016/j.lfs.2020.117425. Epub 2020 Feb 11.
Ref 2 Amentoflavone attenuates cell proliferation and induces ferroptosis in human gastric cancer by miR-496/ATF2 axis. Chem Biol Drug Des. 2023 Oct;102(4):782-792. doi: 10.1111/cbdd.14288. Epub 2023 Jul 16.
Ref 3 Amentoflavone promotes ferroptosis by regulating reactive oxygen species (ROS) /5'AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) to inhibit the malignant progression of endometrial carcinoma cells. Bioengineered. 2022 May;13(5):13269-13279. doi: 10.1080/21655979.2022.2079256.