BCI-632, also known as MGS0039, is a selective mGlu2 and 3 receptor antagonist licensed from Taisho Pharmaceutical Co. Ltd. It is a competitive orthosteric inhibitor with equal functional potency (~20nM) on mGlu2 and 3. It is in vivo active in many models used to measure anti-depressive or pro-cognitive activity. The compound has good plasma protein binding but relative poor permeability which leads to low oral bioavailability in animal models as well as in humans. In humans at the doses given, BCI-632 was well tolerated and could be developed in an intravenous or subcutaneous formulation to treat treatment resistant depression (TRD).
BCI-838 is the lead oral prodrug of BCI-632 also licensed from Taisho Pharmaceutical Co. Ltd. BCI-838 has improved oral bioavailability, high protein binding and converts reasonably well to BCI-632 in the plasma. Repeat dose toxicity studies in one rodent and one non-rodent species have shown an excellent safety profile. A phase 1 study in normal subjects has been completed. The primary indications for BCI-838 are TRD as well as major depressive disorder (MDD) and Alzheimer’s disease (AD).
BCI-1038, BCI-1206, BCI-1283
BrainCells is evaluating three additional prodrugs with improved in vitro properties compared to BCI-838 to further increase plasma conversion in humans. A Phase 1 minidose study has been completed.