1G244

1G244 is a potent DPP8/9 inhibitor with IC50s of 12 nM and 84 nM, respectively. 1G244 does not inhibit DPPIV and DPPII. 1G244 induces apoptosis in multiple myeloma cells and has anti-myeloma effects[1][2].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Metabolic Enzyme/Protease >> Dipeptidyl Peptidase

IC50: 12 nM (DPP8), 84 nM (DPP9)[2]

1G244 (0-100 μM; 72 hours; Delta47, U266 , KMS-5, RPMI8226, or MM.1 S cells) treatment dose-dependently decreases viable cell number of five multiple myeloma cell lines[1]. 1G244 (50 μM; 0-48 hours; MM.1 S cells) treatment induces apoptosis, as cleaved forms of both caspase-3 and PARP are detected[1]. Cell Viability Assay[1] Cell Line: Delta47, U266 , KMS-5, RPMI8226, or MM.1 S cells Concentration: 0 μM, 1 μM, 5 μM, 10 μM, 50 μM, or 100 μM Incubation Time: 72 hours Result: Dose-dependently decreased viable cell number of five multiple myeloma cell lines. Western Blot Analysis[1] Cell Line: MM.1 S cells Concentration: 50 μM Incubation Time: 0 hour, 3 hours, 6 hours, 12 hours, 24 hours, 48 hours Result: Decreased caspase-3 and PARP protein.

1G244 (30 mg/kg; subcutaneous injection; once-a-week; for 3 weeks; NOG female mice) treatment apparently suppresses the subcutaneous growth of MM.1 S cells in murine xenograft model[1]. Animal Model: NOD/Shi-scid IL-2Rγnull (NOG) female mice (6-7 weeks; 19-21 g) injected with MM.1 S cells[1] Dosage: 30 mg/kg Administration: Subcutaneous injection; once-a-week; for 3 weeks Result: Apparently suppressed the subcutaneous growth of MM.1 S cells in murine xenograft model.

[1]. Sato T, et al. DPP8 is a novel therapeutic target for multiple myeloma. Sci Rep. 2019 Dec 2;9(1):18094.

[2]. Leen Heirbaut, et al. Probing for improved selectivity with dipeptidederived inhibitors of dipeptidyl peptidases 8 and 9: the impact of P1-variation. MedChemComm. 2016, 7.