GNF-156 (ganaplacide or KAF-156) is an antimalarial agent that is part of the imidazolopiperazine family. It exerts activity against pre-erythrocytic liver stages, asexual and sexual blood stages. An improvement compared to existing antimalarial drug combinations is that this compound shows promising single-dose antimalarial activity, and no serious safety and tolerability concerns in humans are known so far. Phase II clinical trials have been completed for GNF-156. Its potential is also being investigated in combination with lumefantrine (an aryl-amino alcohol) in LUM-KAF156.

Tofimilast is a potent phosphodiesterase-4 (PDE4) inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/ml. Tofimilast exhibited an apparent slower absorption through the rat lung after administration as a dry powder, although absorption half-life values were <1 h and therefore the significance of a formulation effect for this compound is questionable. Tofimilast was tested as a therapeutic agent against asthma and chronic obstructive pulmonary disease but development has been discontinued due to lack of efficacy.

NLG919 is a novel small-molecule IDO-pathway inhibitor. NLG919 potently inhibits this pathway in vitro and in cell-based assays. It is orally bioavailable and has a favorable pharmacokinetic and toxicity profile. In mice, a single oral administration of NLG919 reduces the concentration of plasma and tissue Kyn by ∼ 50%. Using IDO-expressing human monocyte-derived DCs in allogeneic MLR reactions, NLG919 potently blocked IDO-induced T cell suppression and restored robust T cell responses with an ED50=80 nM. Similarly, using IDO-expressing mouse DCs from tumor-draining lymph nodes, NLG919 abrogated IDO-induced suppression of antigen-specific T cells (OT-I) in vitro. In vivo, in mice bearing large established B16F10 tumors, administration of NLG919 markedly enhanced the anti-tumor responses of naïve, resting pmel-1 cells to vaccination with cognate hgp100 peptide plus CpG-1826 in IFA