Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0028)
Name
Brucine
Synonyms
BRUCINE; 357-57-3; 10,11-Dimethoxystrychnine; Brucinum; 2,3-Dimethoxystrychnine; (-)-Brucine; l-Brucine; 2,3-Dimethoxystrychnidin-10-one; Strychnidin-10-one, 2,3-dimethoxy-; 10,11-Dimethystrychnine; Brucine, Anhydrous; Brucina; Brucin; 6NG17YCK6H; Brucine alkaloid; CHEBI:3193; DTXSID2024662; Dimethoxy strychnine; Brucine hydrate; NSC-757797; Bruzin; 2,3-Dimethoxy-strychnine; RCRA waste number P018; Strychnine, 2,3-dimethoxy-; DTXCID204662; 145428-94-0; Brucin [German]; Brucina [Italian]; CAS-357-57-3; SMR000112281; 63428-84-2; 5892-11-5; UNII-6NG17YCK6H; 10,11-dimethoxy strychnine; CCRIS 4754; HSDB 307; anhydrous brucine; Bisdesmethylbrucin; UN 1570; NCGC00094861-01; EINECS 206-614-7; UN1570; BRUCINE [VANDF]; BRUCINUM [HPUS]; BRUCINE [HSDB]; BRUCINE [MI]; RCRA waste no. P018; Brucine, anhydrous, 98%; BRUCINE [NFLIS-DRUG]; GTPL342; MLS000515808; MLS001424166; SCHEMBL113229; CHEMBL501756; MEGxp0_001865; ACon1_001990; Brucine [UN1570] [Poison]; RRKTZKIUPZVBMF-IBTVXLQLSA-N; HMS2052O03; HMS2268L16; Tox21_111349; Tox21_302174; BDBM50401037; AKOS015955678; AKOS024282466; CCG-101078; NC00328; NSC 757797; NCGC00255253-01; NCGC00263445-02; NCGC00384497-01; B0670; B0946; C09084; Q411022; SR-01000712407; Q-100426; SR-01000712407-5; BRD-K68077509-001-01-6; Brucine, European Pharmacopoeia (EP) Reference Standard; (1R,11S,18S,20R,21R,22S)-4,5-dimethoxy-12-oxa-8,17-diazaheptacyclo[15.5.2.0^{1,18}.0^{2,7}.0^{8,22}.0^{11,21}.0^{15,20}]tetracosa-2(7),3,5,14-tetraen-9-one

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Status
Investigative
Drug Type
Small molecular drug
Structure
Formula
C23H26N2O4
IUPAC Name
(4aR,5aS,8aR,13aS,15aS,15bR)-10,11-dimethoxy-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one
Canonical SMILES
COC1=C(C=C2C(=C1)C34CCN5C3CC6C7C4N2C(=O)CC7OCC=C6C5)OC
InChI
InChI=1S/C23H26N2O4/c1-27-16-8-14-15(9-17(16)28-2)25-20(26)10-18-21-13-7-19-23(14,22(21)25)4-5-24(19)11-12(13)3-6-29-18/h3,8-9,13,18-19,21-22H,4-7,10-11H2,1-2H3/t13-,18-,19-,21-,22-,23+/m0/s1
InChIKey
RRKTZKIUPZVBMF-IBTVXLQLSA-N
PubChem CID
442021
TTD Drug ID
D0H2UT
Full List of Ferroptosis Target Related to This Drug
NADPH oxidase 4 (NOX4)
 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 
Responsed Regulator Cyclic AMP-dependent transcription factor ATF-3 (ATF3) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U118 cells Astrocytoma Homo sapiens CVCL_0633
U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
A-172 cells Glioblastoma Homo sapiens CVCL_0131
In Vivo Model
The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times.

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Response regulation Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT to prevent H2O2 degradation on the other hand.
Cystine/glutamate transporter (SLC7A11)
 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 Glioblastoma ICD-11: 2A00
 Disease Info 
Responsed Regulator Cyclic AMP-dependent transcription factor ATF-3 (ATF3) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model U118 cells Astrocytoma Homo sapiens CVCL_0633
U87 MG-Red-Fluc cells Glioblastoma Homo sapiens CVCL_5J12
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
A-172 cells Glioblastoma Homo sapiens CVCL_0131
In Vivo Model
The athymic BALB/c nude mice (4 weeks; 20-22 g; Beijing Vital River Laboratory Animal Technology Company, China) were housed in a specific pathogen-free environment under a 12-h lightdark cycle with free access to food and water. The animals were allowed to acclimatize to their surroundings for 3 days. U87 cells (1 x 106) in the logarithmic growth phase in 100 uL PBS were subcutaneously injected into the right flank. Therapeutic experiments were started when the tumor reached around 150 mm3 after about 10 days. Mice were allocated to receive intraperitoneal injections of vehicle (control group, n = 6) or 40 mg/kg bodyweight (n = 6) in the same volume (50 uL) once a day for 13 times.

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Response regulation Brucine inhibited glioma cell growth in vitro and in vivo, and brucine induced ATF3 upregulation and translocation into nuclei via activation of ER stress. ATF3 promoted brucine-induced H2O2 accumulation via upregulating NOX4 and SOD1 to generate H2O2 on one hand, and downregulating catalase and xCT (SLC7A11) to prevent H2O2 degradation on the other hand.
References
Ref 1 ATF3 contributes to brucine-triggered glioma cell ferroptosis via promotion of hydrogen peroxide and iron. Acta Pharmacol Sin. 2021 Oct;42(10):1690-1702. doi: 10.1038/s41401-021-00700-w. Epub 2021 Jun 10.