RK-287107

RK-287107 is a potent and specific tankyrase inhibitor with IC50s of 14.3 and 10.6 nM for tankyrase-1 and tankyrase-2, respectively. RK-287107 blocks colorectal cancer cell growth[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> PARP

Signaling Pathways >> Cell Cycle/DNA Damage >> PARP

tankyrase-1:14.3 nM (IC50)

tankyrase-2:10.6 nM (IC50)

RK-87107 (0.01-10 μM; 12 hours) shows an antiproliferative effect on colorectal cancer cells harboring short adenomatous polyposis coli (APC) mutations. The 50% growth inhibition (GI50) value of RK-287107 on COLO-320DM cells is 0.449 μM[1]. RK-287107 (0.03-10 μM; 16 hours) causes accumulation of tankyrase and Axin1/2[1]. RK-287107 (0.03-10 μM; 16 hours) also downregulates β-catenin signaling in cultured cells[1]. Cell Proliferation Assay[1] Cell Line: Colorectal cancer COLO-320DM, SW403, RKO, HCC2998, HCT-116, and DLD-1 cells Concentration: 0.01, 0.1, 1, 10 μM Incubation Time: 12 hours Result: Inhibited the growth of APC-mutated (β-catenin-dependent) colorectal cancer COLO-320DM and SW403 cells. The GI50 value of RK-287107 on COLO-320DM is 0.449 μM. Did not inhibit the growth of APC-wild (β-catenin-independent) colorectal cancer cell lines, including RKO, HCT-116, HCC2998 and DLD-1. Western Blot Analysis[1] Cell Line: COLO-320DM cells Concentration: 0.03, 0.1, 0.33, 1, 3, and 10 μM Incubation Time: 16 hours Result: Downregulation of active β-catenin was observed

RK-287107 (100 and 300 mg/kg; i.p. administration; once per day; 5-days on/ 2-days off schedule for 2 weeks) inhibits tumor growth in a mouse xenograft model[1]. Animal Model: 6-week-old female NOD.CB17-Prkdcscid/J mice with colorectal cancer COLO-320DM[1] Dosage: 100 and 300 mg/kg Administration: Administration i.p.; once per day; 5-days on/ 2-days off schedule for 2 weeks Result: 100 and 300 mg/kg resulted in 32.9% and 44.2% TGI, respectively.

[1]. Mizutani A, et al. RK-287107, a potent and specific tankyrase inhibitor, blocks colorectal cancer cell growth in a preclinical model. Cancer Sci. 2018 Dec;109(12):4003-4014.