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. 2015 Nov 13;5:15182. doi: 10.1038/srep15182

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Copyright © 2015, Macmillan Publishers Limited

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(a) Pten deficient murine prostate cancer cells (CaP8) show poor responsiveness to escalating doses of enzalutamide, IC₅₀ = 22.84 (μM), but are (b,c) highly sensitive to OP449 (CaP8 IC₅₀= 0.42 μM, Myc-CaP IC₅₀= 0.9 μM). (d) OP449 is a potent inhibitor of PI3K/Akt signaling in Pten deficient murine prostate cancer (CaP8) cells. In vitro treatment (8 hours) with OP449 reduced PI3K-Akt signaling in CaP8 cells corresponding with (e) reduced in vivo PI3K-Akt signaling and CRPC progression in Pten mutant prostates (Pb-Cre⁺;Pten^L/L, castrate) (OP449 10 mg/kg, SQ, q.a.d., commenced at 6 wks). (f) Proliferating (Ki67+) cells were reduced (p < 0.01) in OP449 treated mutants.