Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0283)
Name
Cephalosporin
Synonyms
CEPHALOSPORIN; CHEMBL1235646; Q27465008; (2R)-2-[(R)-{[(6R)-6-amino-6-carboxyhexanoyl]amino}(carboxy)methyl]-5-methylidene-5,6-dihydro-2H-1,3-thiazine-4-carboxylic acid; REC

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Status
Approved
Drug Type
Small molecular drug
Structure
Formula
C15H21N3O7S
IUPAC Name
(2R)-2-[(R)-[[(6R)-6-amino-6-carboxyhexanoyl]amino]-carboxymethyl]-5-methylidene-2H-1,3-thiazine-4-carboxylic acid
Canonical SMILES
C=C1CSC(N=C1C(=O)O)C(C(=O)O)NC(=O)CCCCC(C(=O)O)N
InChI
InChI=1S/C15H21N3O7S/c1-7-6-26-12(18-10(7)14(22)23)11(15(24)25)17-9(19)5-3-2-4-8(16)13(20)21/h8,11-12H,1-6,16H2,(H,17,19)(H,20,21)(H,22,23)(H,24,25)/t8-,11+,12-/m1/s1
InChIKey
JGKXEMYIHDYWCZ-JFUSQASVSA-N
PubChem CID
25058126
TTD Drug ID
D07JVS
Full List of Ferroptosis Target Related to This Drug
Heme oxygenase 1 (HMOX1)
 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/Suppressor
Responsed Disease Nasopharyngeal cancer ICD-11: 2B6B
 Disease Info 
Pathway Response Ferroptosis hsa04216
MAPK signaling pathway hsa04010
Apoptosis hsa04210
Cell Process Cell ferroptosis
Cell apoptosis
Cell proliferation
In Vitro Model A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
XWLC-05 cells Lung adenocarcinoma Homo sapiens CVCL_IQ71
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SGC-7901 cells Gastric carcinoma Homo sapiens CVCL_0520
CNE2 cells Normal Homo sapiens CVCL_6889
U-251MG cells Astrocytoma Homo sapiens CVCL_0021
MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
K-562 cells Chronic myelogenous leukemia Homo sapiens CVCL_0004
ECV-304 cells Bladder carcinoma Homo sapiens CVCL_2029
In Vivo Model
6-8 week old male balb/cnude micewere purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). Nasopharyngeal carcinoma CNE2 cells were collected during logarithmic growth and rinsed with PBS twice and resuspended to a density of 1 x 107 cells/ml using fresh and cooled DMEM/F12 medium (free of FBS and antibiotics). Each mouse was inoculated subcutaneously with a 0.1 ml cell suspension on the right-side flank. Tumor-bearing mice were used for in vivo anticancer studies 8 days after inoculation when the average tumor volume reached ~200 mm3.

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Response regulation Cephalosporin antibiotics showed highly specific and selective anticancer activity on nasopharyngeal carcinoma CNE2 cells both in vitro and vivo with minimal toxicity. Pathway analyses indicate apoptotic and the ErbB-MAPK-p53 signaling pathways are significantly enriched. HMOX1 represents the top one ranked upregulated gene by COS and overlaps with 16 of 42 enriched apoptotic signaling pathways. Inhibition of HMOX1 significantly reduced the anticancer efficacy of cefotaxime in CNE2 cells.
References
Ref 1 Cephalosporin antibiotics specifically and selectively target nasopharyngeal carcinoma through HMOX1-induced ferroptosis. Life Sci. 2021 Jul 15;277:119457. doi: 10.1016/j.lfs.2021.119457. Epub 2021 Apr 5.