IPR-803

IPR-803 is a potent inhibitor of the uPAR•uPA protein-protein interaction (PPI). IPR-803 binds directly to uPAR with sub-micromolar affinity. IPR-803 displays anti-tumor activity[1].

Research Areas >> Cancer

Ki: 0.2 μM (PPI)[1]

IPR-803 blocks invasion of breast cancer cells line MDA-MB-231, and inhibits matrix metalloproteinase (MMP) breakdown of the extracellular matrix (ECM)[1]. IPR-803 impairs MDA-MB-231 cell adhesion and migration[1]. IPR-803 induces a concentration-dependent impairment of cell adhesion with an IC50 of approximately 30 μM[1]. IPR-803 inhibits MDA-MB-231 cells growth with an IC50 of 58 μM[1]. IPR-803 (0-200 μM; 3 days) blocks the invasion of MDA-MB-231 cells, and most of the inhibition of cell invasion is unlikely due to cytotoxicity of the compound[1]. IPR-803 (1-50 μM; 24 hours) does not have a significant effect on apoptosis or necrosis[1]. IPR-803 (50 μM; 30 minutes) shows inhibition of MAPK phosphorylation[1]. Cell Proliferation Assay[1] Cell Line: MDA-MB-231 cells Concentration: 0 μM, 50 μM, 150 μM, 200 μM Incubation Time: 3 days Result: Displays 90 percent blockage of invasion that is observed at 50 μM.

IPR-803 (200 mg/kg; i.g.; three times a week; for 5 weeks) impairs breast cancer metastasis, but no statistical significance to the differences in body weight between treated and untreated[1]. IPR-803 has a low oral bioavailability at 4 percent, and remains high concentration even after 10 hours in tumor tissue[1]. IPR-803 exhibits a half-life (t1/2) of 5 hours[1]. Animal Model: NSG mice with MDA-MB-231 cells xenograft[1] Dosage: 200 mg/kg Administration: Oral gavage; three times a week; for 5 weeks Result: Impaired metastasis to the lungs. Animal Model: NOD/SCID mice[1] Dosage: 200 mg/kg (Pharmacokinetic Study) Administration: Oral administration Result: t1/2=5 hours.

[1]. Mani T, et al. Small-molecule inhibition of the uPAR•uPA interaction: synthesis, biochemical, cellular, in vivo pharmacokinetics and efficacy studies in breast cancer metastasis. Bioorg Med Chem. 2013 Apr 1;21(7):2145-55.