Products

35G8 PDI inhibitor RGNCY-0084

$795.00 (AUD)
Per 10 mg

202M 10d

Formula

small molecule

Tags

autophagy small molecule glioma Glioblastoma RGNCY-0084 35G8 PDI Nrf2 SLC7A11 TXNIP ferroptosis

Description

35G8 is a novel nanomolar PDI (protein disulfide isomerase) inibitor that is toxic in a panel of human glioblastoma cell lines,  PDI is overexpressed in glioblastoma and folds nascent protein responsible for the progression and spread of this brain cancer.  35G8 induces nuclear factor-like 2 (Nrf2) anti-oxidant response, endoplasmic reticulum  stress response and autophagy.  35G8 upregulates heme oxygenase 1 and solute carrier family 7 member 11 (SLC7A11) transcription and protein expression and repressed PDI target genes including thioredoxin-interacting protein 1 (TXNIP) and early growth respoinse 1 (EGFR1).  35G8 indices cell death via autophagy and ferroptosis rather than apoptosis or necrosis.  35G8 can be used as chemical probe to validate PDI as a target for brain tumor therapy.  Insulin turbidity assay IC50 = 170+10nM.


Systematic Name: 1,3,6-trimethylpyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione
SMILES: CC1=NN(C)C(C2=N1)=NC(N(C)C2=O)=O
Formula: C8H9N5O2
Mol Wt:  207.08
PMID:  29235250


References

Kyani A et al. Discovery and Mechanistic Elucidation of a Class of Protein Disulfide Isomerase Inhibitors for the Treatment of Glioblastoma. ChemMedChem 2018, 13, 164 – 177.

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