Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0267)
Name
Isorhynchophylline
Synonyms
Isorhynchophylline; 6859-01-4; Isorhyncophylline; 7-Isorhyncophylline; Isorhychophylline; 7F4P99KHLJ; CHEBI:70071; UNII-7F4P99KHLJ; methyl (E)-2-[(3S,6'R,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate; (16E,20-alpha)-16,17-Didehydro-17-methoxy-2-oxo-corynoxan-16-carboxylic acid; Corynoxan-16-carboxylic acid, 16,17-didehydro-17-methoxy-2-oxo-, methyl ester, (16E,20-alpha)-; Rel-methyl (E)-2-((3S,6'R,7'S,8a'S)-6'-ethyl-2-oxo-2',3',6',7',8',8a'-hexahydro-5'H-spiro[indoline-3,1'-indolizin]-7'-yl)-3-methoxyacrylate; 39032-62-7; IsoRhy; MLS000728608; CHEMBL480521; SCHEMBL23259272; HMS2267O23; HMS3886F22; HY-N0766; BDBM50531282; BP0799; s9310; AKOS025402306; AC-7996; CCG-268459; CS-3805; AS-75287; SMR000470794; C16980; Q-100013; ISORHYNCHOPHYLLINE (CONSTITUENT OF CAT'S CLAW); Q27138409; ISORHYNCHOPHYLLINE (CONSTITUENT OF CAT'S CLAW) [DSC]; CORYNOXAN-16-CARBOXYLIC ACID, 16,17-DIDEHYDRO-17-METHOXY-2-OXO-, METHYL ESTER, (16E,20.ALPHA.)-; CORYNOXAN-16-CARBOXYLIC ACID, 16,17-DIDEHYDRO-17-METHOXY-2-OXO-, METHYL ESTER, (16E,20alpha)-; methyl (2E)-2-[(3S,6'R,7'S,8'aS)-6'-ethyl-2-oxo-1,2,3',5',6',7',8',8'a-octahydro-2'H-spiro[indole-3,1'-indolizin]-7'-yl]-3-methoxyprop-2-enoate; SPIRO(3H-INDOLE-3,1'(5'H)-INDOLIZINE)-7'-ACETIC ACID, 6'-ETHYL-1,2,2',3',6',7',8',8'A-OCTAHYDRO-.ALPHA.-(METHOXYMETHYLENE)-2-OXO-, METHYL ESTER, (.ALPHA.E,1'S,6'R,7'S,8'AS)-; SPIRO(3H-INDOLE-3,1'(5'H)-INDOLIZINE)-7'-ACETIC ACID, 6'-ETHYL-1,2,2',3',6',7',8',8'A-OCTAHYDRO-alpha-(METHOXYMETHYLENE)-2-OXO-, METHYL ESTER, (alphaE,1'S,6'R,7'S,8'AS)-; Spiro[3H-indole-3,1'(5'H)-indolizine]-7'-acetic acid,6'-ethyl-1,2,2',3',6',7',8',8'a-octahydro-a-(methoxymethylene)-2-oxo-,methyl ester, (aE,1'S,6'R,7'S,8'aS)-

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Structure
Formula
C22H28N2O4
IUPAC Name
methyl (E)-2-[(3S,6'R,7'S,8'aS)-6'-ethyl-2-oxospiro[1H-indole-3,1'-3,5,6,7,8,8a-hexahydro-2H-indolizine]-7'-yl]-3-methoxyprop-2-enoate
Canonical SMILES
CCC1CN2CCC3(C2CC1C(=COC)C(=O)OC)C4=CC=CC=C4NC3=O
InChI
InChI=1S/C22H28N2O4/c1-4-14-12-24-10-9-22(17-7-5-6-8-18(17)23-21(22)26)19(24)11-15(14)16(13-27-2)20(25)28-3/h5-8,13-15,19H,4,9-12H2,1-3H3,(H,23,26)/b16-13+/t14-,15-,19-,22-/m0/s1
InChIKey
DAXYUDFNWXHGBE-VKCGGMIFSA-N
PubChem CID
3037048
Full List of Ferroptosis Target Related to This Drug
Cystine/glutamate transporter (SLC7A11)
 Target Info 
In total 2 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Intracerebral hemorrhage ICD-11: 8B00
 Disease Info 
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
p53 signaling pathway hsa04115
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection).

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Response regulation Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.
Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Intracerebral hemorrhage ICD-11: 8B00
 Disease Info 
Responsed Regulator hsa-miR-122-5p (miRNA) Suppressor
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
p53 signaling pathway hsa04115
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HT22 cells Normal Mus musculus CVCL_0321
In Vivo Model
Adult male Sprague-Dawley rats (SD rats, weighing 250-300 g) aged 11-12 weeks were purchased from SLAC Laboratory Animal Co., Ltd. (Shanghai, China). All 96 rats were randomly divided into four groups of 24 rats each: Sham group, Sham + IRN (30 mg/Kg) group, ICH group, and ICH + IRN (30 mg/Kg) group. The rats in sham group were injected with PBS solution, and the Sham + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection) after the sham operation. After ICH, the rats in ICH group were injected with PBS solution, and the ICH + IRN (30 mg/Kg) group was received an equal amount of 30 mg/Kg IRN solution (intra-peritoneal injection).

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Response regulation Isorhynchophylline (IRN) decreased ferroptosis and lipid ROS level, upregulated the expression of miR-122-5p and SLC7A11 mRNA, and inhibited TP53 expression. In conclusion, IRN protects neurocyte from intracerebral hemorrhage (ICH)-induced ferroptosis via miR-122-5p/TP53/SLC7A11 pathway, which may provide a potential therapeutic mechanism for ICH.
References
Ref 1 Isorhynchophylline Relieves Ferroptosis-Induced Nerve Damage after Intracerebral Hemorrhage Via miR-122-5p/TP53/SLC7A11 Pathway. Neurochem Res. 2021 Aug;46(8):1981-1994. doi: 10.1007/s11064-021-03320-2. Epub 2021 May 3.