Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0350)
Name
FIN56
Synonyms
FIN56; 1083162-61-1; N2,N7-dicyclohexyl-9-(hydroxyimino)-9H-fluorene-2,7-disulfonamide; FIN 56; FIN-56; 2-N,7-N-Dicyclohexyl-9-hydroxyiminofluorene-2,7-disulfonamide; FIN56;FIN 56; SCHEMBL21460308; CHEBI:176419; BCP29145; s8254; AKOS034831611; CCG-269836; CS-7632; BS-14396; HY-103087; C71305; A920909; N,N'-dicyclohexyl-9-(hydroxyimino)-9H-fluorene-2,7-disulfonamide; N(2),N(7)-dicyclohexyl-9-(hydroxyimino)-9H-fluorene-2,7-disulfonamide

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Structure
Formula
C25H31N3O5S2
IUPAC Name
2-N,7-N-dicyclohexyl-9-hydroxyiminofluorene-2,7-disulfonamide
Canonical SMILES
C1CCC(CC1)NS(=O)(=O)C2=CC3=C(C=C2)C4=C(C3=NO)C=C(C=C4)S(=O)(=O)NC5CCCCC5
InChI
InChI=1S/C25H31N3O5S2/c29-26-25-23-15-19(34(30,31)27-17-7-3-1-4-8-17)11-13-21(23)22-14-12-20(16-24(22)25)35(32,33)28-18-9-5-2-6-10-18/h11-18,27-29H,1-10H2
InChIKey
JLCFMMIWBSZOIS-UHFFFAOYSA-N
PubChem CID
118986699
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 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 Bladder cancer ICD-11: 2C94
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model J82 cells Bladder carcinoma Homo sapiens CVCL_0359
253J cells Bladder carcinoma Homo sapiens CVCL_7935
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
RT-112 cells Bladder carcinoma Homo sapiens CVCL_1670
mEFs (Mouse embryonic fibroblasts)
Response regulation Fin56, a type 3 inducer, leads to ferroptosis mainly by promoting GPX4 degradation. Fin56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Glioblastoma ICD-11: 2A00
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model LN-229 cells Glioblastoma Homo sapiens CVCL_0393
U118 cells Astrocytoma Homo sapiens CVCL_0633
In Vivo Model
1x105 LN229 cells were injected subcutaneously into the right shoulder of 4-week-old nude mice (SLAC laboratory animal Center; Shanghai, China). 2 weeks later, nude mice (n = 10) were divided into two groups, control group and FIN56 treatment group. Subcutaneous tumors were harvested 30 days after treatment. Tumors were fixed and paraffin-embedded for immunohistochemistry.

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Response regulation FIN56 decreased cell viability, inhibited cell proliferation and caused cell cycle arrest on gliomaLN229 and U118 cells. Further study showed that FIN56 induced ferroptosis and induced lysosomal membrane permeabilization in a ferroptosis and transfactor EB dependent manner. Animal study demonstrated that FIN56 inhibited glioma growth and caused ferroptosisin vivo.
References
Ref 1 Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells. Cell Death Dis. 2021 Oct 29;12(11):1028. doi: 10.1038/s41419-021-04306-2.
Ref 2 FIN56, a novel ferroptosis inducer, triggers lysosomal membrane permeabilization in a TFEB-dependent manner in glioblastoma. J Cancer. 2021 Sep 13;12(22):6610-6619. doi: 10.7150/jca.58500. eCollection 2021.