TABLE 2 

Enantioselectivity of Kpuu and SLC13 inhibition in transfected cells and human hepatocytes for an enantiomer pair, PF-06649298 (R) and PF-06649297 (S), and PF-06761281 (R)

Cell TypesPF-06649298 (R)PF-06649297 (S)PF-06761281 (R)
IC50KpuuIC50KpuuIC50Kpuu
μMμMμM
Parental HEK293ND0.1ND0.1NDBLQ
Human SLC13A5 HEK2930.4129>250.60.511727
Human SLC13A2 HEK293>1000.1>25ND131.5
Human SLC13A3 HEK293>1000.2>25ND1411
Human hepatocyte164.8>250.40.7436
  • Methods for IC50 measurement were reported previously (Huard et al., 2015, 2016). Kpuu in HEK293 transfected cells was measured at cell density of 1 million cells/ml, 0.5 μM test compound concentration, and 1-hour incubation time.

  • BLQ, below limit of quantification; ND, not determined.