biostudies-literatureLapadula DNHLBI NIH HHSNCI NIH HHSNIHNIGMS NIH HHS963-973https://www.ebi.ac.uk/biostudies/studies/S-EPMC6445713biostudies-literatureUnknown17(4)Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to the liver, leaving patients with few options. Recurrent activating mutations in the G proteins, Gα_q and Gα₁₁, are observed in approximately 93% of all uveal melanomas. Although therapeutic intervention of downstream Gα_q/11 targets has been unsuccessful in treating uveal melanoma, we have found that the Gα_q/11 inhibitor, FR900359 (FR), effectively inhibits oncogenic Gα_q/11 signaling in uveal melanoma cells expressing either mutant Gα_q or Gα₁₁. Inhibition of oncogenic Gα_q/11 by FR results in cell-cycle arrest and induction of apoptosis. Furthermore, colony formation is prevented by FR treatment of uveal melanoma cells Molecular cancer research : MCREffects of Oncogenic Gα_q and Gα₁₁ Inhibition by FR900359 in Uveal Melanoma.PMC6445713P30CA056036R01 CA218024R01 GM088242R01 GM056444R03 CA202316P30 CA056036P01 HL114471R01 GM56444R01 CA109182F31 CA225064F31 CA224803McGrath DBenovic JLRandolph CEZhou NFarias ETall GGAplin AEWedegaertner PBZhang LAguirre-Ghiso JTerai MSato TLapadula DWu SPurwin TJCharpentier THfalseEffects of Oncogenic Gα_q and Gα₁₁ Inhibition by FR900359 in Uveal Melanoma.Uveal melanoma is the most common intraocular tumor in adults and often metastasizes to the liver, leaving patients with few options. Recurrent activating mutations in the G proteins, Gα_q and Gα₁₁, are observed in approximately 93% of all uveal melanomas. Although therapeutic intervention of downstream Gα_q/11 targets has been unsuccessful in treating uveal melanoma, we have found that the Gα_q/11 inhibitor, FR900359 (FR), effectively inhibits oncogenic Gα_q/11 signaling in uveal melanoma cells expressing either mutant Gα_q or Gα₁₁. Inhibition of oncogenic Gα_q/11 by FR results in cell-cycle arrest and induction of apoptosis. Furthermore, colony formation is prevented by FR treatment of uveal melanoma cells 2019-01-01T00:00:00Z2019 Apr2026-03-15T21:01:52.747Z2025-08-13T03:06:17.71ZS-EPMC64457133056797210.1158/1541-7786.mcr-18-057410.1158/1541-7786.MCR-18-0574