GDC-0425 (RG-7602) is an orally administered, selective small molecule inhibitor targeting checkpoint kinase 1 (ChK1), utilized in research focused on various malignancies [1] [2].

Inhibition of MEK either by pharmacologic inhibitors or RNAi-mediated gene silencing significantly protected cells from reduced viability upon GDC-0425 treatment [3]. GDC-0425 (3 μM; 24 hours) treatment results the hyperphosphorylation of Chk1 [3]. Cell Viability Assay [3] Cell Line: Chk1-positive breast cancer cell lines Concentration: 0.001, 0.01, 0.1, 1, 10 mM Incubation Time: 72 hours Result: Reduced cell proliferation. Cell Viability Assay [3] Cell Line: U-2 OS cells Concentration: 3 μM Incubation Time: 24 hours Result: Led to hyperphosphorylation of Chk1.

GDC-0425 shows partial suppression of tumor growth. The Gemcitabine/GDC-0425 combination results in significant tumor regression in all tested models [3]. Animal Model: NCr nude mice bearing xenografts of both osteosarcoma and triple-negative breast cancer models (143B PML BK TK, HCC1806, and HCC70 cell lines) [3] Dosage: For the 4-arm study, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination for 15 days. For 6-arm studies of HCC1806 and HCC70 models, mice were treated with vehicle, Gemcitabine 120 mg/kg, GDC-0425 50 mg/kg, GDC-0425 75 mg/kg alone, or Gemcitabine and GDC-0425 combination. Administration: Orally administrated at 24, 48, and 72 hours after gemcitabine administration by intraperitoneal injection. Result: Exhibited partial suppression of tumor growth upon treatment with either Gemcitabine or GDC-0425 alone. Notably, the Gemcitabine/GDC-0425 combination resulted in significant tumor regression in all tested models.