NCGC00378430

• CAT Number: I044581
• CAS Number: 920650-00-6
• Molecular Formula: C22H23N3O5S
• Molecular Weight: 441.50
• Purity: ≥95%
• Synonyms: N-(4-methoxy-3-morpholin-4-ylsulfonylphenyl)-3-pyrrol-1-ylbenzamide
• InChI: InChI=1S/C22H23N3O5S/c1-29-20-8-7-18(16-21(20)31(27,28)25-11-13-30-14-12-25)23-22(26)17-5-4-6-19(15-17)24-9-2-3-10-24/h2-10,15-16H,11-14H2,1H3,(H,23,26)
• InChIKey: IFXCVBOQNYHBMX-UHFFFAOYSA-N
• SMILES: COC1=C(C=C(C=C1)NC(=O)C2=CC(=CC=C2)N3C=CC=C3)S(=O)(=O)N4CCOCC4

NCGC00378430 is a potent SIX1/EYA2 interaction inhibitor. NCGC00378430 partially reverses transcriptional and metabolic profiles mediated by SIX1 overexpression and reverses SIX1-induced TGF-β signaling and epithelial-mesenchymal transition (EMT). NCGC00378430 inhibits SIX1-mediated breast cancer metastasis in a mouse model[1].
NCGC00378430 is a potent SIX1/EYA2 interaction inhibitor with an IC50 of 52 μM in the Alphascreen assay[1]. ?
NCGC00378430 (20 μM; 3 days) blocks TGF-β induced activation of p-Smad3, upregulation of FN1, and downregulation of E-CAD in T47D cells[1]. ?
NCGC00378430 (10 μM; 3 days) reverses the Sine oculis homeobox homolog 1 (SIX1)-induced increase in p-SMAD3 and does not alter total E-CAD levels. NCGC00378430 restores membranous E-CAD in MCF7-SIX1 cells, along with inhibiting FN1 expression[1]. ?
NCGC00378430 (10 or 20 μM) disrupts SIX1-EYA2 interaction in breast cancer cells (MCF7, T47D, MDA-MB-231 cells)[1]. ?
NCGC00378430 (10 μM; for 3 days) partially reverses SIX1-mediated transcriptional and metabolic signatures in MCF7 breast tumor cells[1].
NCGC00378430 (25 mg/kg; local injection to the site of tumor; every other day; from day 3 until the day 21) dramatically decreases distant metastatic burden compared to vehicle treatment[1]. ?
NCGC00378430 (20 mg/kg; IV) has a T1/2α of 0.25 hours[1].

Reference

[1]. Hengbo Zhou, et al. Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis. Cancer Res. 2020 Jun 15;80(12):2689-2702.
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