ASR-490

ASR-490 reduces the viability of HCT116 and SW620 cells by downregulating Notch1 signaling. ASR-490 overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants. ASR-490 inhibits the tumor growth in control (pCMV/HCT116) and Notch1/HCT116 in xenotransplanted mice[1].

Research Areas >> Cancer

Signaling Pathways >> Stem Cell/Wnt >> Notch

Notch1[1]

ASR-490 (0-1.6 µM; 24 h, 48 h) reduces the viability of HCT116 and SW620 cells in 24h (IC50 =750 nM in HCT116 cells, IC50 =1.2 µM in SW620 cells) and 48h (IC50 =600 nM in HCT116 cells, IC50 =850 nM in SW620 cells)[1].ASR-490 (750 nM in HCT116 cells and 1.2 µM in SW620 cells, 24 h) shows apoptotic cell death and upregulation of the proapoptotic markers Bax and cleaved PARP Expression; inhibits the capability of colorectal cancer cells[1].ASR-490 (HCT116 cells; 750 nM in 24 h, 600 nM in 48 h) overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants[1]. Cell Viability Assay[1] Cell Line: HCT116, SW620 cells Concentration: 0-1.6 µM Incubation Time: 24 h, 48 h Result: Reduced the viability of HCT116 and SW620 cells in 24h (IC50 =750 nM in HCT116 cells, IC50 =1.2 µM in SW620 cells) and 48h (IC50 =600 nM in HCT116 cells, IC50 =850 nM in SW620 cells). Apoptosis Analysis[1] Cell Line: HCT116, SW620 cells Concentration: 750 nM in HCT116 cells and 1.2 µM in SW620 cells Incubation Time: 24 h Result: Showed apoptotic cell death and upregulation the proapoptotic markers Bax and cleaved PARPExpression, inhibited the capability of colorectal cancer cells. Cell Proliferation Assay[1] Cell Line: HCT116 cells Concentration: 750 nM in 24 h, 600 nM in 48 h Incubation Time: 24 h, 48 h Result: Overcome Notch1 overexpression and inhibited the growth of HCT/Notch1 transfectants.

ASR-490 (5 mg/kg; i.p.; thrice a week for 4 weeks) inhibits the tumor growth in control (pCMV/HCT116) and Notch1/HCT116 in xenotransplanted mice[1]. Animal Model: Six- to 8-week-old BALB/c athymic nude mice (nu/nu) (pCMV/HCT116and Notch1/HCT116 (C4) xenografts)[1]. Dosage: 5 mg/kg Administration: i.p., thrice a week for 4 weeks Result: Inhibited the tumor growth in control (pCMV/HCT116) and Notch1/HCT116 in xenotransplanted mice.

[1]. Tyagi A, et al. ASR490, a Small Molecule, Overrides Aberrant Expression of Notch1 in Colorectal Cancer. Mol Cancer Ther. 2020; 19(12):2422-2431.