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Chemical Structure| 1083162-61-1 Chemical Structure| 1083162-61-1

Structure of FIN56
CAS No.: 1083162-61-1

Chemical Structure| 1083162-61-1

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FIN56 is a ferroptosis activator and glutathione peroxidase 4 (GPX4) degradation inducer. It also bound to and activated squalene synthase (SQS), an enzyme involved in isoprenoid biosynthesis.

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Cen, Si-Yu ; Lin, Fang ; Li, Xuan ; Hu, Yanglin ; Liu, Jin-Pin ; Xue, Zian , et al.

Abstract: Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Purchased from AmBeed:

Liu, Jin-Pin ; Cen, Si-Yu ; Xue, Zian ; Wang, Tian-Xiang ; Gao, Yun ; Zheng, Jia , et al.

Abstract: Ferroptosis is a nonapoptotic form of cell death characterized by iron-dependent lipid peroxidation and has been implicated in multiple pathological conditions. Glutathione peroxidase 4 (GPX4) plays an essential role in inhibiting ferroptosis by eliminating lipid peroxide using glutathione (GSH) as a reductant. In this study, we found Ellman’s reagent DTNB and a series of disulfide compounds, including disulfiram (DSF), an FDA-approved drug, which protect cells from erastin-induced ferroptosis. Mechanistically, DTNB or DSF is conjugated to multiple cysteine residues in GPX4 and disrupts GPX4 interaction with HSC70, an adaptor protein for chaperone mediated autophagy, thus preventing GPX4 degradation induced by erastin. In addition, DSF ameliorates concanavalin A induced acute liver injury by suppressing ferroptosis in a mouse model. Our work reveals a novel regulatory mechanism for GPX4 protein stability control. We also discover disulfide compounds as a new class of ferroptosis inhibitors and suggest therapeutic repurposing of DSF in treating ferroptosis-related diseases.

Purchased from AmBeed: ; ; ; 83150-76-9 ; 1360705-96-9 ; ; 56-59-7

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Product Details of FIN56

CAS No. :1083162-61-1
Formula : C25H31N3O5S2
M.W : 517.66
SMILES Code : O=S(C1=CC(C2=NO)=C(C3=C2C=C(S(=O)(NC4CCCCC4)=O)C=C3)C=C1)(NC5CCCCC5)=O
English Name :N2,N7-Dicyclohexyl-9-(hydroxyimino)-9H-fluorene-2,7-disulfonamide
MDL No. :MFCD30480929
InChI Key :JLCFMMIWBSZOIS-UHFFFAOYSA-N
Pubchem ID :118986699

Safety of FIN56

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.66mL

1.93mL

0.97mL

19.32mL

3.86mL

1.93mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

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