INTRODUCTION: @entity1468 remains a major cause of maternal and fetal morbidity and mortality. Despite intensive research over the last 50 years, significant therapeutic advances have yet to be realised. We recently reported on the role of activin A in the pathophysiology of @entity1468 , whereby a @entity1468 state was induced in pregnant @entity19 through activin A infusion. Using the same animal model, the effects of inhibiting activin A signalling on this @entity1468 state have now been assessed with low molecular weight compounds structurally related to activin-receptor-like kinase (ALK) inhibitors. METHODS: 23 synthetic compounds were screened for ability to reduce activin A-induced free radical production in HUVECs. Further, following administration of activin A (50  g) via a subcutaneous mini-osmotic pump from day 10 of pregnancy, the most active inhibitor, @entity17311 -140A, (1 mg/kg) was also concomitantly administered via subcutaneous injections. RESULTS: Significant reductions in activin A-induced systolic blood pressure and urine albumin: @entity1011 ratio were observed with inhibitor-treated animals. However, these findings were accompanied by sustained elevation of liver enzymes and albumin extravasation in the brains of pregnant @entity19 that received @entity17311 -140A. Furthermore, inhibition of activin A signalling with @entity17311 -140A failed to rescue fetal growth restriction, and treatment with @entity17311 -140A alone resulted in craniofacial and karyotypic abnormalities. DISCUSSION: These data indicate that whilst inhibition of activin A signalling by the low molecular weight ALK kinase inhibitor, @entity17311 -140A, reduced some of the physiological manifestations of @entity1468 , the potential for serious maternal and fetal side effects may preclude it from clinical applications.

Inhibition of activin A signalling in a XXXX model of @entity1468 .

@entity19 :: ('10090', 'Species') :: ['mice'] @entity1468 :: ('MESH:D011225', 'Disease') :: ['pre-eclampsia-like disease', 'pre-eclampsia', 'Pre-eclampsia'] @entity17311 :: ('19252(Tax:10090)', 'Gene') :: ['MKP-1'] @entity1011 :: ('MESH:D003404', 'Chemical') :: ['creatinine']
@entity19 :: (10090,Species) :: ['mouse']
