Ravoxertinib (benzenesulfonate)

Ravoxertinib benzenesulfonate (GDC-0994 benzenesulfonate) is an orally active ERK1/2 inhibitor. Ravoxertinib benzenesulfonate inhibits the ERK1/2 MAPK signaling pathway and reduces the expression levels of c-Myc, HK2 and LDHA. Ravoxertinib benzenesulfonate decreases mammosphere formation, and exerts additive and/or superadditive cytotoxicity when combined with Ipatasertib (HY-15186) in 3D tumor sphere models. Ravoxertinib benzenesulfonate can be used in research related to various cancers including breast cancer, melanoma, head and neck cancer, non-small cell lung cancer, ovarian cancer and Merkel cell carcinoma^[1][2][3][4]. IC50 & Target:IC50: 6.1 nM (ERK1), 3.1 nM (ERK2), 12 nM (p90RSK)^[1] In Vitro:In relevant in vitro experiments on stem cell-like human glioma stem cells, Ravoxertinib benzenesulfonate completely abrogates Humanin (HY-P1928)-induced Temozolomide (HY-17364) resistance, restores the growth inhibitory effect of Temozolomide on tumor cells, and inhibits the Humanin-induced upregulation of Hus1 protein expression^[1].
Combination of Ravoxertinib (0.1-10 μM; 7 d) benzenesulfonate and ipatasertib induces additive to superadditive cytotoxicity in multiple human tumor organoid spheres, with over 2-log cell killing achieved in the 417821-307-R-J1 lung squamous cell carcinoma organoid spheres^[2].
Ravoxertinib (1 μM; 72 h) benzenesulfonate does not significantly inhibit the LMCD1-mediated enhancement of cell proliferation in human dermal fibroblasts^[3]. In Vivo:Ravoxertinib (20-30 mg/kg; p.o.) benzenesulfonate is well tolerated at 20 mg/kg and 30 mg/kg in NSG mice bearing 171881-019-R-J1 breast carcinoma PDX, but its combination with ipatasertib does not control tumor growth, leading to progressive disease^[2].
Ravoxertinib (20-30 mg/kg; p.o.) benzenesulfonate is well tolerated at 20 mg/kg and 30 mg/kg in NSG mice bearing 845751-090-R-J2 head and neck squamous cell carcinoma PDX, but its combination with ipatasertib does not control tumor growth, leading to progressive disease^[2].