1. Apoptosis
  2. Ferroptosis
  3. Ferroptosis-IN-22

Ferroptosis-IN-22 is a selective ferroptosis inhibitor by targeting NCOA4 and disrupting its interaction with ferritin with an EC50 of 520 nM and a Kd of 0.78 μM. Ferroptosis-IN-22 has a strong inhibitory activity against ferroptosis induced by multiple ferroptosis inducers (RSL3 (HY-100218A), Erastin (HY-15763), ML210 (HY-100003), FIN56 (HY-103087)), but does not inhibit necrosis induced by H2O2 or apoptosis induced by STS (HY-15141). Ferroptosis-IN-22 effectively ameliorates Concanavalin A (HY-P2149)-induced acute liver injury. Ferroptosis-IN-22 can be used for the study of ferroptosis-related diseases.

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Ferroptosis-IN-22

Ferroptosis-IN-22 Chemical Structure

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Description

Ferroptosis-IN-22 is a selective ferroptosis inhibitor by targeting NCOA4 and disrupting its interaction with ferritin with an EC50 of 520 nM and a Kd of 0.78 μM. Ferroptosis-IN-22 has a strong inhibitory activity against ferroptosis induced by multiple ferroptosis inducers (RSL3 (HY-100218A), Erastin (HY-15763), ML210 (HY-100003), FIN56 (HY-103087)), but does not inhibit necrosis induced by H2O2 or apoptosis induced by STS (HY-15141). Ferroptosis-IN-22 effectively ameliorates Concanavalin A (HY-P2149)-induced acute liver injury. Ferroptosis-IN-22 can be used for the study of ferroptosis-related diseases[1].

In Vitro

Ferroptosis-IN-22 (Compound 4k) exhibits anti-ferroptotic activity with EC50 values were 0.515 μM (RSL3) and 2.776 μM (Erastin) in HT-1080 cells, 0.4061 μM (RSL3) and 1.308 μM (Erastin) in 786-O cells, and 0.093 μM (RSL3) and 1.013 μM (Erastin) in MDA-MB-231 cells, and also suppresses ferroptosis induced by ML210 and FIN56[1].
Ferroptosis-IN-22 (4-8 μM) significantly reduced RSL3 or Erastin induced lipid peroxidation in both HT-1080 and 786-O cells and does not have direct antioxidative activity[1].
Ferroptosis-IN-22 (4 μM, 6 h) directly binds to NCOA4, a key receptor protein in ferritin autophagy, disrupting the interaction between NCOA4 and ferritin (FTH1), thereby inhibiting the ferritin autophagy process rather than relying on direct iron chelation in HT-1080 cells[1].
Ferroptosis-IN-22 demonstrates low cardiotoxicity and minimal risk of CYP-mediated drug-drug interactions (DDIs)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis[1]

Cell Line: HT-1080 cells
Concentration: 4 μM
Incubation Time: 6 h
Result: Significantly reduced the amount of FTH1/FTL co-precipitated with NCOA4.
Parmacokinetics[1]
Species Dose Route Indicator value
Rat 10 mg/kg p.o. T1/2 3.751 h
Rat 5 mg/kg i.v. T1/2 4.009 h
Rat 10 mg/kg p.o. Tmax 2.000 h
Rat 5 mg/kg i.v. Tmax 0.083 h
Rat 10 mg/kg p.o. Cmax 557.082 ng/mL
Rat 5 mg/kg i.v. Cmax 61139.150 ng/mL
Rat 10 mg/kg p.o. AUC0-t 1474.816 ng·h/mL
Rat 5 mg/kg i.v. AUC0-t 30464.355 ng·h/mL
Rat 10 mg/kg p.o. AUC0-∞ 1498.461 ng·h/mL
Rat 5 mg/kg i.v. AUC0-∞ 30509.903 ng·h/mL
Rat 10 mg/kg p.o. MRT0-t 2.961 h
Rat 5 mg/kg i.v. MRT0-t 0.645 h
Rat 10 mg/kg p.o. MRT0-∞ 3.263 h
Rat 5 mg/kg i.v. MRT0-∞ 0.689 h
Rat 10 mg/kg p.o. F 2.421 %
Rat 5 mg/kg i.v. Vss 113.508 mL/kg
Rat 5 mg/kg i.v. Vd 941.525 mL/kg
Rat 5 mg/kg i.v. CL 164.535 mL/h/kg
In Vivo

Ferroptosis-IN-22 (Compound 4k) (5-15 mg/kg, i.p., 2 doses before ConA injection) alleviates Concanavalin A (ConA) (HY-P2149)-Induced acute liver injury by ferroptosis inhibition[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: ConA induced acute liver injury model established in C57BL/6J mice[1]
Dosage: 5 and 15 mg/kg
Administration: Intraperitoneal injection (i.p.), 24 hours and 0.5 hours before ConA injection
Result: Decreased serum ALT and AST levels and improved liver tissue injury.
Significantly reduced the mRNA levels of TNF-α and IL-6, two major inflammatory cytokines in the liver.
Effectively reduced the levels of4-HNE and MDA, two lipid peroxidation products, in liver tissues.
Showed no effect on the morphology and the 4-HNE level of other vital organs including kidney, spleen, heart and lung.
Reduced the mRNA expression of ferroptosis marker Ptgs2.
Molecular Weight

393.48

Formula

C27H23NO2

SMILES

OC1=C(C(C)(C)C)C=C(C2=C(C3=CC=CC=C3)C=C(C4=CC=CC=C4)N=C2O5)C5=C1

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Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation
References
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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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Product Name:
Ferroptosis-IN-22
Cat. No.:
HY-175869
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