Mannose 6-phosphate (M6P) has type-I integral membrane receptors. M6P-receptors bind and transport M6P-enzymes to lysosomes, but it can also modulate the activity of a variety of extracellular M6P-glycoproteins (i.e., latent TGFbeta precursor, urokinase-type plasminogen activator receptor, Granzyme B, growth factors, Herpes virus). M6P has been demonstrated to reduce active TGF-β1 expression on cultured tendon fibroblasts and improved range of movement in a rabbit flexor tendon injury model. Studies of M6P in relation to skin scarring demonstrate improvement in scar cosmesis and accelerated return of normal dermal architecture. Juvidex, a formulation of M6P, inhibits the activation of TGF-beta1 and TGF-beta2, which are present at high levels in adult wounds that scar. On the other hands, M6P in a 600 mM hypertonic solution (Adaprev) potentially acts via a physical, non-chemical, hyperosmotic effect.

Totrombopag is an orally bioavailable, nonpeptide, small-molecule thrombopoietin receptor agonist. It induces proliferation and differentiation of megakaryocytes and progenitor cells, ultimately increasing the production of platelets. Totrombopag has been investigated in healthy volunteers in a phase 1, single-blind, randomized fashion to cause a dosedependent increase in platelet count with demonstrated safety. There were no serious adverse events, no significant changes in laboratory or cardiovascular safety parameters and there was no observed relationship between the incidence or severity of adverse events and dose. Most adverse events were mild in intensity and self-limiting. Totrombopag was developed for the treatment of immune thrombocytopenic purpura.