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Chemical Structure| 927822-86-4 Chemical Structure| 927822-86-4

Structure of KC7F2
CAS No.: 927822-86-4

Chemical Structure| 927822-86-4

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KC7F2 is a selective HIF-1α transcription inhibitor with IC50 of 20 μM in a cell-based assay.

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

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Product Citations

Product Citations

Wang, Shengnan ; Chen, Youfang ; Sun, Zhendong ; Zeng, Yafen ; Wang, Guidan ; Lin, Qingfan , et al.

Abstract: Sepsis-associated encephalopathy (SAE) is a common and debilitating complication of sepsis, yet its cellular mechanisms and targeted therapies remain unclear. Microglia preserve neuroinflammatory homeostasis and neural circuit integrity through efferocytosis, but how this process is altered in SAE and regulated by immunometabolism is poorly defined. Here, we investigated the molecular basis of microglial efferocytosis impairment using LPS-stimulated BV2 cells and a cecal ligation and puncture (CLP) murine SAE model. We integrated RNA sequencing, HIF-1α and SLC7A11 gain- and loss-of-function approaches and in vitro functional assays. In vivo, HIF-1α was pharmacologically inhibited (KC7F2) or stabilized (DMOG) to evaluate its role in SAE. We assessed microglial efferocytosis and polarization, neuronal and synaptic integrity, cognition, survival, and brain metabolomics. LPS induced a pro-inflammatory microglial phenotype and reduced efferocytosis mediators (Tyro3, Mertk, Axl), impairing clearance of apoptotic neurons. HIF-1α upregulation interacted with SLC7A11 to suppress the TAM-Rac1-NCKAP1 axis, leading to efferocytic failure; knockdown of HIF-1α or SLC7A11 restored efferocytosis. In CLP mice, HIF-1α/SLC7A11 elevation coincided with TAM-Rac1-NCKAP1 suppression. These results reveal that impaired microglial efferocytosis is a key but overlooked feature in SAE. restored efferocytosis, shifted cytokines toward anti-inflammatory profiles, improved cognition and survival, and normalized metabolomic signatures, while produced opposite effects. This work uncovers a previously unknown HIF-1α-SLC7A11 pathway driving microglial dysfunction in SAE, offering fresh insight into disease mechanisms and pointing to HIF-1α as a promising therapeutic target.

Keywords: Sepsis-associated encephalopathy ; Microglia ; Efferocytosis ; HIF-1α ; SLC7A11 ; TAM receptors ; Metabolic reprogramming

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Product Details of KC7F2

CAS No. :927822-86-4
Formula : C16H16Cl4N2O4S4
M.W : 570.38
SMILES Code : O=S(C1=CC(Cl)=CC=C1Cl)(NCCSSCCNS(C2=CC(Cl)=CC=C2Cl)(=O)=O)=O
English Name :N,N'-(Disulfanediylbis(ethane-2,1-diyl))bis(2,5-dichlorobenzenesulfonamide)
MDL No. :MFCD22683809
InChI Key :REQLACDIZMLXIC-UHFFFAOYSA-N
Pubchem ID :16047442

Safety of KC7F2

Related Pathways of KC7F2

epigenetics

Isoform Comparison

Biological Activity

Target
  • HIF

    HIF-1α, IC50:20 μM

  • HIF1

    HIF-1α, IC50:20 μM

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.75mL

0.35mL

0.18mL

8.77mL

1.75mL

0.88mL

17.53mL

3.51mL

1.75mL

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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