Ferroptosis-centered Drug Response Information
General Information of the Drug (ID: ferrodrug0301)
| Name |
Solasonine
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| Synonyms |
Solasonine; 19121-58-5; Tomatine solaradixine; Solasonin; alpha-Solasonine; CHEBI:9191; TR60638HXL; C45H73NO16; .alpha.-Solasonine; EINECS 242-826-6; beta-D-Galactopyranoside, (3beta,22alpha,25R)-spirosol-5-en-3-yl O-6-deoxy-alpha-L-mannopyranosyl-(1-2)-O-(beta-D-glucopyranosyl-(1-3))- (9CI); UNII-TR60638HXL; NSC-82149; NSC 82149; PURAPURINE; SOLASONINE [MI]; CHEMBL438956; SCHEMBL2683980; QCTMYNGDIBTNSK-XEAAVONHSA-N; DTXSID801028790; AKOS030528257; CCG-270555; AC-33986; BS-16392; S9144; Q7557107; (2S,3R,4R,5R,6S)-2-[(2R,3R,4S,5S,6R)-5-hydroxy-6-(hydroxymethyl)-2-[(1S,2S,4S,5'R,6R,7S,8R,9S,12S,13R,16S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2'-piperidine]-16-yl]oxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-3-yl]oxy-6-methyloxane-3,4,5-triol; .BETA.-D-GALACTOPYRANOSIDE, (3.BETA.,22.ALPHA.,25R)-SPIROSOL-5-EN-3-YL O-6- DEOXY-.ALPHA.-L-MANNOPYRANOSYL-(1-2)-O-(.BETA.-D-GLUCOPYRANOSYL-(1-3))-; .BETA.-D-GALACTOPYRANOSIDE, (3.BETA.,22.ALPHA.,25R)-SPIROSOL-5-EN-3-YL O-6-DEOXY-.ALPHA.-L-MANNOPYRANOSYL-(1->2)-O-(.BETA.-D-GLUCOPYRANOSYL-(1->3))-; beta-D-Galactopyranoside, (3beta,22alpha,25R)-spirosol-5-en-3-yl O-6-deoxy-alpha-L-mannopyranosyl-(1-->2)-O-[beta-D-glucopyranosyl-(1-->3)]-; beta-D-Galactopyranoside, (3beta,22alpha,25R)-spirosol-5-en-3-yl O-6-deoxy-alpha-L-mannopyranosyl-(1-2)-O-(beta-D-glucopyranosyl-(1-3))-
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| Structure |
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3D MOL
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| Formula |
C45H73NO16
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| IUPAC Name |
(2S,3R,4R,5R,6S)-2-[(2R,3R,4S,5S,6R)-5-hydroxy-6-(hydroxymethyl)-2-[(1S,2S,4S,5'R,6R,7S,8R,9S,12S,13R,16S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icos-18-ene-6,2'-piperidine]-16-yl]oxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-3-yl]oxy-6-methyloxane-3,4,5-triol
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| Canonical SMILES |
CC1CCC2(C(C3C(O2)CC4C3(CCC5C4CC=C6C5(CCC(C6)OC7C(C(C(C(O7)CO)O)OC8C(C(C(C(O8)CO)O)O)O)OC9C(C(C(C(O9)C)O)O)O)C)C)C)NC1
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| InChI |
InChI=1S/C45H73NO16/c1-19-8-13-45(46-16-19)20(2)30-27(62-45)15-26-24-7-6-22-14-23(9-11-43(22,4)25(24)10-12-44(26,30)5)57-42-39(61-40-36(54)34(52)31(49)21(3)56-40)38(33(51)29(18-48)59-42)60-41-37(55)35(53)32(50)28(17-47)58-41/h6,19-21,23-42,46-55H,7-18H2,1-5H3/t19-,20+,21+,23+,24-,25+,26+,27+,28-,29-,30+,31+,32-,33+,34-,35+,36-,37-,38+,39-,40+,41+,42-,43+,44+,45-/m1/s1
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| InChIKey |
QCTMYNGDIBTNSK-XEAAVONHSA-N
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| PubChem CID | |||||
Full List of Ferroptosis Target Related to This Drug
Cystine/glutamate transporter (SLC7A11)
| 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 | Pancreatic cancer | ICD-11: 2C10 | |||
| Responsed Regulator | Transcription factor AP-2-alpha (TFAP2A) | Suppressor | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Ferroptosis | hsa04216 | ||||
| Apoptosis | hsa04210 | ||||
| Ubiquitin mediated proteolysis | hsa04120 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| Cell proliferation | |||||
| Cell migration | |||||
| Cell invasion | |||||
| In Vitro Model | PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | |
| CFPAC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_1119 | ||
| In Vivo Model |
For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment.
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| Response regulation | Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis. | ||||
| Experiment 2 Reporting the Ferroptosis-centered Drug Act on This Target | [1] | ||||
| Target for Ferroptosis | Suppressor | ||||
| Responsed Disease | Pancreatic cancer | ICD-11: 2C10 | |||
| Responsed Regulator | Ubiquitin thioesterase OTUB1 (OTUB1) | Suppressor | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Ferroptosis | hsa04216 | ||||
| Apoptosis | hsa04210 | ||||
| Ubiquitin mediated proteolysis | hsa04120 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell apoptosis | |||||
| Cell proliferation | |||||
| Cell migration | |||||
| Cell invasion | |||||
| In Vitro Model | PANC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_0480 | |
| CFPAC-1 cells | Pancreatic ductal adenocarcinoma | Homo sapiens | CVCL_1119 | ||
| In Vivo Model |
For xenograft assays, we subcutaneously injected 1 x 106 PANC-1 and CFPAC-1 into the right side of each male nude mouse (n = 6). Tumor volumes (length x width2 x 0.5) were measured at specified time points. For one treatment cycle in a week (starting from week 1 to week 5), solasonine (40 or 80 mg/kg, oral administration, 2 times) were given. A total of five treatment cycles were conducted in this experiment.
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| Response regulation | Solasonine is involved in ferroptosis by suppressing TFAP2A-mediated transcriptional upregulation of OTUB1, thereby activating ubiquitinated degradation of SLC7A11 and promoting pancreatic cancer cell ferroptosis. | ||||
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
| In total 1 item(s) under this Target | |||||
| Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target | [2] | ||||
| Target for Ferroptosis | Suppressor | ||||
| Responsed Disease | Hepatocellular carcinoma | ICD-11: 2C12 | |||
| Pathway Response | Fatty acid metabolism | hsa01212 | |||
| Ferroptosis | hsa04216 | ||||
| Cell Process | Cell ferroptosis | ||||
| Cell proliferation | |||||
| Cell migration | |||||
| Cell invasion | |||||
| In Vitro Model | Hep-G2 cells | Hepatoblastoma | Homo sapiens | CVCL_0027 | |
| HepaRG cells | Hepatocellular carcinoma | Homo sapiens | CVCL_9720 | ||
| In Vivo Model |
BALB/c nude mice aged 4-6 weeks, weighing 15~20 g, were purchased from Shanghai SLAC Laboratory Animal Co.,Ltd (Shanghai, China). Following acclimation, the right flank of each experimental mouse was subcutaneously injected with HepG2 cells (2 x 106) suspended in PBS (200 uL) and then randomly assigned to: (i) the control group and received no further treatment or (ii) the intervention group and received solasonine (50 mg/kg body weight) in an equal volume of PBS. Tumor volumes were measured every 5 days. After 30 days, the mice were sacrificed and the tumors were resected, weighed, and processed for histological analysis.
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| Response regulation | Solasonine increased lipid ROS levels in HepG2 cells by suppression of GPX4 and GSS. However, the use of a ferroptosis inhibitor reversed solasonine-induced ROS production and cell apoptosis. Taken together, solasonine promotes ferroptosis of hepatocellular carcinoma cells via GPX4-induced destruction of the glutathione redox system. | ||||
References