Fig. 5: In vivo PK/PD/efficacy of AZ’6421 in CTC174 PDX model.
From: Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC
a–c CTC174 xenografts grown in female NSG mice were dosed once or twice daily for 4 days with vehicle, AZ’6421, or AZD9833 at the doses shown. a Tumour tissues were harvested 6 h after the last dose for analysis of ERα protein levels by immunoblotting. ERα levels were normalised to vinculin control and expressed as a % of the mean vehicle control. b Free plasma exposure for AZ’6421 over the ERα DC90 achieved at 100 mg/kg. c Tumour tissues were harvested 6 hours after the last dose for analysis of PGR mRNA expression levels by qPCR. PGR expression was normalised to beta-actin control and expressed as a percentage (%) of the mean vehicle control. d CTC174 xenografts grown in female NSG mice were dosed once or twice daily with the compounds as shown. Tumour growth was measured by caliper at regular intervals, individual tumour volumes plotted and the mean indicated with lines for each dosed group. All error bars indicate ± s.e.m.
