Imlunestrant (LY 3484356) is a potent, oral, selective estrogen receptor degrader (SERD) and pure estrogen receptor antagonist with Ki values of 0.64 nM and 2.8 nM against WT ERα and Y537S mutant ERα proteins, respectively.
LY 3484356 is a potent and highly efficient degrader of wild type ERα and Y537N mutant ERα proteins in cells, with IC50 values 3.0 nM and 9.6 nM, respectively.
LY3484356 is also a potent inhibitor of ERα-mediated transcription in vitro and in vivo.
LY 3484356 inhibits cell proliferation in wild type ERα and ESR1 Y537N mutant breast cancer cell lines with IC50 of 3 and 17 nM, respectively. LY3484356 has IC50 of <100 nM against a panel of ER+ breast cancer cell lines.
LY3484356 has demonstrated sustained and prolonged target inhibition in ESR1 wild type (MCF7) and ESR1 Y537S mutant (ST941/C) xenograft tumors.
LY3484356 demonstrated significant tumor growth inhibition and tumor regressions in wild type ESR1 breast cancer xenograft models such as MCF7, T47D and ZR-75-1, as well as ESR1 mutant breast cancer PDX models.
LY3484356 has shown synergy or additivity in combination with CDK4/6 inhibitor abemaciclib, mTOR inhibitor everolimus and PIK3CA inhibitor alpelisib in inhibiting cell proliferation in ER+ breast cancer cell lines in vitro and tumor growth inhibition in relevant xenograft or PDX models in vivo.