DMUP

DMUP is a potent CD47-SIRPα axis inhibitor. DMUP induces apoptosis and increases the macrophage phagocytosis in A549 cells. DMUP decreases the expression of CD47 and SIRPα protein. DMUP shows antitumor activity[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

DMUP (72 h) shows antiproliferative activity with IC50s of 0.92, 3.58, 6.29, 1.54 µM for A549, A549/DDP, PANC-1, HepG2 cells, respectively[1]. DMUP (5 µM, 24 h) arrests the cell cycle in S phase in A549 cells[1]. DMUP (5 µM, 48 h) induces apoptosis in A549 cells[1]. DMUP (5 µM, 24 h) decreases the expression of CD47 and SIRPα protein[1]. DMUP (5 µM, 4 h) increases the macrophage phagocytosis in A549-GFP cells[1]. Cell Proliferation Assay[1] Cell Line: A549, A549/DDP, PANC-1, HepG2 cells Concentration: 0-64 µM Incubation Time: 72 h Result: Showed antiproliferative activity with IC50s of 0.92, 3.58, 6.29, 1.54 µM for A549, A549/DDP, PANC-1, HepG2 cells, respectively. Cell Cycle Analysis[1] Cell Line: A549 cells Concentration: 5 µM Incubation Time: 24 h Result: Arrested the cell cycle in the S phase. Apoptosis Analysis[1] Cell Line: A549 cells Concentration: 5 µM Incubation Time: 48 h Result: Induced cell apoptosis. Western Blot Analysis[1] Cell Line: A549, THP-1 cells Concentration: 5 µM Incubation Time: 24 h Result: Decreased the expression of CD47 and SIRPα protein.

DMUP (10 mg/kg, i.v., every other day for 17 day) shows antitumor activity[1]. DMUP (5, 10, 20, 40 mg/kg, i.v.,every two days for 18 days) shows no toxicity in mice[1]. Animal Model: ICR mice[1] Dosage: 5, 10, 20, 40 mg/kg Administration: i.v., every two days, 18 days Result: Showed low toxicity with LD50 of greater than 20 mg/kg. Animal Model: A549 xenograft BALB/c nude mice[1] Dosage: 10 mg/kg Administration: i.v., every other day, 17 day Result: Showed antitumor activity.

[1]. Tan Y, et al. Platinum(IV) complexes as inhibitors of CD47-SIRPα axis for chemoimmunotherapy of cancer. Eur J Med Chem. 2022; 229:114047.