RLY-2608 is an orally active first-in-class allosteric mutant-selective inhibitor of PI3Ka with anti-tumor activity. RLY-2608 inhibits tumor growth in PIK3CA-mutant xenograft mice models with minimal impact on insulin.
RLY-2608 (1 nM-100 μM, 5 days) inhibits the proliferation and phosphorylated AKT (pAKT) in PIK3CA mutant cancer cell lines independent of the hotspot mutation[2].
RLY-2608 (25-100 mg/kg, p.o., twice a day for 50 days) inhibits tumors in tumor xenograft mice models with reduced impact on insulin levels[1].RLY-2608 (12.5-100 mg/kg, p.o., a single dose for 4 days) demonstrates potent tumor growth inhibition in Balb/c nude female mice bearing HSC-2 tumors[2].
References:
[1]. Andreas Varkaris, et al. Discovery and clinical proof-of-concept of RLY-2608, a first-in-class mutant-selective allosteric PI3Ka inhibitor that decouples anti-tumor activity from perinsulinemia. Cancer Discov. 2023 Nov 2.
[2]. Pazolli E, et al. RLY-2608: the first allosteric mutant-and isoform-selective inhibitor of PI3Kα, is efficacious as a single agent and drives regressions in combination with standard of care therapies in PIK3CA mutant breast cancer models[J]. Cancer Res., 2022, 82. [3]. Perez C A, et al. First-in-human global multi-center study of RLY-2608, a pan-mutant and isoform-selective PI3Kα inhibitor, as a single agent in patients with advanced solid tumors and in combination with fulvestrant in patients with advanced breast cancer[J]. 2022.