OM-153 is a potent and orally active tankyrase inhibitor with IC50s of 13 nM and 2 nM for tankyrase 1 and tankyrase 2 (TNKS1/2), respectively. OM-153 inhibits luciferase-based Wnt/β-catenin signaling reporter activity with an IC50 value of 0.63 nM. OM-153 shows inhibition of Wnt/β-catenin signaling and proliferation in COLO 320DM[1][2].
OM-153 shows picomolar IC50 inhibition (0.63 nM) in a cellular (HEK293) WNT/β-catenin signaling reporter assay, no off-target liabilities, overall favorable absorption, distribution, metabolism, and excretion (ADME) properties, and an improved pharmacokinetic profile in mice[1].
OM-153 decreases cell growth in COLO 320DM cells with a GI50 value of 10 nM and a GI25 value of 2.5 nM (concentrations resulting in 50% and 25% growth inhibition, respectively), while cell growth in RKO cells was insubstantially affected by the treatment[2].
OM-153 inhibits WNT/β-catenin, YAP, and MYC signaling and shows an antiproliferative fffect in human cancer cell lines[2].
OM-153 (0.1-10 mg/kg; p.o.; twice daily; for 34 days) reduces WNT/β-catenin signaling and tumor progression in COLO 320DM colon carcinoma xenografts[2].
OM-153 potentiates anti-PD-1 immune checkpoint inhibition and antitumor effect in a B16-F10 mouse melanoma model[2].
| Animal Model: | CB17-SCID mice bearing COLO 320DM cells[2] |
| Dosage: | 10 mg/kg, 3.3 mg/kg, 1 mg/kg, 0.33 mg/kg, or 0.1 mg/kg |
| Administration: | p.o.; twice daily; for 34 days |
| Result: | Reduced WNT/β-catenin signaling and tumor progression in COLO 320DM colon carcinoma xenografts. |
| Animal Model: | C57BL/6N mice injected with B16-F10 tumors[2] |
| Dosage: | 10 mg/kg, 1 mg/kg, and 0.1 mg/kg |
| Administration: | p.o.; twice daily; for 20 days |
| Result: | Potentiated anti-PD-1 immune checkpoint inhibition and antitumor effect. |
[1]. Leenders RGG, et al. Development of a 1,2,4-Triazole-Based Lead Tankyrase Inhibitor: Part II. J Med Chem. 2021;64(24):17936-17949.
[2]. Shoshy A. Brinch, et al. The Tankyrase Inhibitor OM-153 Demonstrates Antitumor Efficacy and a Therapeutic Window in Mouse Models. Cancer Research Communications (2022) 2 (4): 233-245.