Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0186)
Name
Levobupivacaine
Synonyms
Levobupivacaine; 27262-47-1; (S)-bupivacaine; (-)-bupivacaine; L(-)-Bupivacaine; Levobupivacaine hydrochloride; Novabupi; (S)-1-Butyl-2',6'-pipecoloxylidide; L-(-)-bupivacaine; (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide; L-bupivacaine; Levobupivacaine free base; (S)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide; Bupivacaine, (s)-; L-(-)-1-Butyl-2',6'-pipecoloxylidide; Bupivacaine, (-)-; Bupivacaine (-)-form; Levobupivacaine (INN); A5H73K9U3W; CHEBI:6149; (2S)-1-butyl-N-(2,6-dimethylphenyl)-2-piperidinecarboxamide; 2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, (2S)-; 27262-47-1 (free base); LEVOBUPIVACAINE [INN]; Levobupivacaine [INN:BAN]; Levobupivacaina; (2~{S})-1-butyl-~{N}-(2,6-dimethylphenyl)piperidine-2-carboxamide; Novabupi (TN); NCGC00159482-02; (S)-(-)-Bupivacaine; UNII-A5H73K9U3W; 2',6'-Pipecoloxylidide, 1-butyl-, L-(-)-; SCHEMBL34537; BIDD:GT0471; LEVOBUPIVACAINE [VANDF]; GTPL7211; LEVOBUPIVACAINE [MART.]; CHEMBL1201193; DTXSID8048496; LEVOBUPIVACAINE [WHO-DD]; LEBVLXFERQHONN-INIZCTEOSA-N; (s)-1-butyl-n-(2,6-dimethylphenyl)-2-piperidinecarboxamide; HY-B0653; BUPIVACAINE (-)-FORM [MI]; BDBM50350791; BDBM50417951; MFCD00936851; s5181; AKOS016340525; DB01002; KS-5195; NCGC00016733-01; NCGC00159482-03; CAS-18010-40-7; CS-0009570; C07887; D08116; D87861; A818983; Q-100344; Q3272027; Z2242128693; (2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboximidic acid; ROPIVACAINE HYDROCHLORIDE MONOHYDRATE IMPURITY A [EP IMPURITY]; OJ0

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C18H28N2O
IUPAC Name
(2S)-1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
Canonical SMILES
CCCCN1CCCCC1C(=O)NC2=C(C=CC=C2C)C
InChI
InChI=1S/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21)/t16-/m0/s1
InChIKey
LEBVLXFERQHONN-INIZCTEOSA-N
PubChem CID
92253
TTD Drug ID
D09QUQ
Full List of Ferroptosis Target Related to This Drug
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 Gastric cancer ICD-11: 2B72
 Disease Info 
Responsed Regulator hsa-miR-489-3p (miRNA) Driver
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model GES-1 cells Normal Homo sapiens CVCL_EQ22
HGC-27 cells Gastric carcinoma Homo sapiens CVCL_1279
SGC-7901 cells Gastric carcinoma Homo sapiens CVCL_0520
In Vivo Model
Ten SCID nude mice aged 6-8 weeks were purchased from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China), and subcutaneously injected with SGC7901 cells (5 x 106 cells per mouse) in left back. One week after feeding, the mice were randomly divided into two groups, the control and treatment group. For the next 25 days, the mice in treatment group were injected with erastin (15 mg/kg intraperitoneally) or co-treated with 40 mol/kg body weight of levobupivacaine once a day. The body weight and tumor size were measured every 3 days.

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Response regulation Levobupivacaine-upregulated miR-489-3p enhanced ferroptosis of gastric cancer cells by targeting SLC7A11. MiR-489-3p was involved in levobupivacaine-induced ferroptosis of gastric cancer cells. Levobupivacaine/miR-489-3p/SLC7A11 axis attenuates gastric cancer cell proliferationin vitro.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
A427 cells Lung carcinoma Homo sapiens CVCL_1055
In Vivo Model
Balb/c nude mice (n= 5, 4-week-old, male) were applied to detect the impact of levobupivacaine on tumor growth. Mice subcutaneously injected with 1 x 107 A549 cells were treated with levobupivacaine (40 umol/Kg) or equal volume saline. The tumor volume was remarked every 5 days and finished at 30 days after injection, followed by the analysis of volume (length (width/2)2) and weight.

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Response regulation Levobupivacaine could inhibit the proliferation and induce the apoptosis of non-small cell lung cancer (NSCLC) cells. Levobupivacaine was able to attenuate the invasion and migration in the cells. The treatment of levobupivacaine remarkably increased the levels of ROS, iron, and Fe2+ in NSCLC cells. Mechanically, levobupivacaine up-regulated the expression of p53 and induced ferroptosis by regulating p53 in NSCLC cells.
References
Ref 1 Levobupivacaine Induces Ferroptosis by miR-489-3p/SLC7A11 Signaling in Gastric Cancer. Front Pharmacol. 2021 Jun 9;12:681338. doi: 10.3389/fphar.2021.681338. eCollection 2021.
Ref 2 Local anesthetic levobupivacaine induces ferroptosis and inhibits progression by up-regulating p53 in non-small cell lung cancer. Aging (Albany NY). 2021 Jun 27;13. doi: 10.18632/aging.203138. Online ahead of print.