RGNCY-0120 (PAWI-2 tumor inhibitor)

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PAWI-2 has inhibitory effects on prostate cancer cells and pancreatic cancer stem cells through a novel mechanism of action involving inhibition of tubulin acetylation, BCL-2 and mitochondrial function.  PAWI-2 inhibits cell proliferation of androgen-sensitive and androgen-insensitive prostate cancer cells (LNCaP and PC-3).  Intraperitoneal administration of PAWI-2 in a PC-3 xenograft model resulted in the inhibition of of tumor growth by 49% compared with vehicle treated mice.  PAWI-2 was demonstrated to synergize with the currently used  clinical treatment, enzalutamide, to inhibit PCa cell viability in vitro and resensitized inhibition of PC-3 tumor growth in vivo.  In addition, PAWI-2 was shown to potently inhibit cell viability and the self-renewal capacity of FGb3 cells, a validated cancer stem cell model (CSC).  PAWI-2 inhibited b3-KRAS signalling independent of KRAS which is clinically significant in tumor progression. PAWI-2 overcame erlotinib (an EGFR inhibitor) resistance in FGB3 cells more potently than bortezomib.  PAWI-2 repreasents a new approach to reverse tumor stemness that resensitizes CSC tumors to drug inhibition.

Systematic Name:  1-(4-((4-methyl-3,4-dihydroquinoxalin-1(2H)-yl)sulfonyl)phenyl)pyrrolidin-2-one


Formula:  C19H21N3O3S

Mol Wt: 371.46

Tags: Cancer, stem cell, Tumor, pancreatic cancer, prostate cancer, RGNCY-0120, PAWI-2, cancer stem cell, PAW