Alobresib

Alobresib (GS-5829) is a BET bromodomain inhibitor, which represents a highly effective therapeutics agent against recurrent/chemotherapy resistant uterine serous carcinoma (USC) overexpressing c-Myc[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BET bromodomain[1]

Alobresib (0.1 nM-100 μM; 72 hours) inhibits cell proliferation in primary uterine serous carcinoma (USC) lines[1]. Cell Proliferation Assay[1] Cell Line: Primary uterine serous carcinoma (USC) lines ARK1 and ARK2 cell lines Concentration: 0.1 nM, 10 nM, 1 μM, 100 μM Incubation Time: 72 hours Result: A progressive, dose response decrease in cell proliferation. IC50s of 27 nM and 31 nM for ARK2 and ARK1 cells, respectively.

Alobresib (10 and 20 mg/kg; oral; twice-daily; for 28 days) impaires USC-ARK2 xenograft tumor growth in female CB17/lcrHsd-Prkd/scid mice. Alobresib exhibits a significantly slower rate of tumor growth in mice, compared with vehicle control and to mice undergoing daily treatment with JQ1 (50 mg/kg/day i.p.)[1]. Alobresib (10 and 20 mg/kg; oral; twice-daily; for 28 days) is well tolerated with no clear impact on body weight compared with vehicle control[1]. Animal Model: Female CB17/lcrHsd-Prkd/scid mice (15-19 g) bearing USC-ARK2 tumors[1] Dosage: 10 and 20 mg/kg Administration: Oral; twice-daily; 28 days Result: Exhibited a significantly slower rate of tumor growth, compared with vehicle control and to mice undergoing daily treatment with JQ1 (50 mg/kg/day i.p.).

[1]. Bonazzoli E, et al. Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer. Clin Cancer Res. 2018 Oct 1;24(19):4845-4853.