SERP
Comments:
As the Ki for the related off-target V1A is ~ 1µM, it is suggested to apply slightly lower maximum test concentration of 300-500 nM. PF- 3274167 has a Ki/Kd of 5-10 nM depending on different literature in a competition assay, but the data for more distal pharmacological readout is missing, e.g. OT-induced intracellular Ca2+-mobilization. The overall selectivity of PF-3274167 is incompletely summarized in a few sentences leaving room for uncertainties and the described SAR covers only 1.5 log units lacking an inactive control from the same chemotype. Depending on the application, alternative oxytocin receptor antagonists are Atosiban, Barusiban, Epelsiban, L-368,899, L-371,257, MSC 1630296, Nolasiban, Retosiban. For in vivo use, no Cmax, AUC or FUB data are given to assess the target engagement and in addition contradictory data are published in 10.1016/j.jsxm.2018.10.008 and 10.1016/j.nucmedbio.2017.07.008 regarding the brain penetration and potential PgP transporter substrate properties. Although the compound might have the potential to study OT pharmacology in vivo, the dose, schedule as well as the route of administration should be investigated further before any kind of recommendation can be given.
(last updated:
23 Nov 2023 )
