Table. 2 Binding, degradation, lipophilicity, and mouse fraction unbound in plasma

From: Metabolism-driven in vitro/in vivo disconnect of an oral ERɑ VHL-PROTAC

Compound

ERα binding IC50 (nM)a

ERα DC50 (nM)

ERα Dmax (%)b

chrom LogD

Mouse fup

AZ’6421 (5)

<0.6 ± 0.2 (5)

0.4 ± 0.1 (8)

100 ± 1 (8)

6.6 ± 0.4 (3)

0.0002 (1)

8

<0.5 ± 0.0 (4)

0.5 ± 0.1 (4)

86 ± 4 (4)

3.8 (2)

0.005 (1)

  1. a) Mixture of sub-nanomolar values and results below tight binding limit.
  2. b) Maximum level of degradation observed for the compound where 0% is vehicle control and 100% is maximal concentration observed for fulvestrant. Data presented is the mean across replicates with standard deviation noted as the ± value. Numerical values in brackets are the number of replicates.
Back to article page