Naroparcil [LF 90055], the lead compound in a series of orally-active antithrombotics, is an analogue of LF 1351, a compound shown to have antithrombotic action. Antithrombotic activity of naroparcil is dependent on modification in the plasma GAG profile which inactivates thrombin via heparin cofactor II (HCII).

Tresperimus is a new stable immunosuppressive analog of 15-deoxyspergualin (DSG) obtained by organic chemical synthesis. It was initially developed as an antitumor agent. Tresperimus has been designed to be chemically stable in aqueous solution. Tresperimus controlled alloreactivity in a fully major histocompatibility complex (MHC) mismatched rat cardiac transplant model and also induced donor-specific long-lasting unresponsiveness. Posttransplant tresperimus therapy effectively protected mice from lethal graft-versus-host disease (GVHD) in a dose-related manner. It has been shown to suppress graft rejection as efficiently as cyclosporine A. Indeed, a short course of tresperimus has similar or better effects compared to the effects of cyclosporine in bone marrow, cardiac, and skin transplant models. Prevention of rejection is related to the induction of donor-specific tolerance without affecting immunity to third-party antigens. In addition, CD4+ T-cells from tresperimus-treated animals can transfer donorspecific tolerance to naive animals, an effect not seen with cyclosporine or other traditional immunosuppressive drugs. The mechanism by which tolerance is induced is not clear. Tresperimus binds to Hsc70, a heat shock protein– chaperoned peptide that, among other effects, inhibits nuclear localization of nuclear factor (NF)-kB, which is required for CD40 and CD28 ligation signaling in antigen-presenting cells, an important early step in T-cell costimulation. Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation. Tresperimus had been in phase III clinical trial for the treatment of graft-versus-host disease. However, this development was discontinued.

Anisperimus [LF 150195] is a deoxyspergualin analogue under development by Fournier Pharma (formerly Groupe Fournier) for the potential treatment of autoimmune disorders and transplant rejection. Anisperimus is a more potent, and less toxic analogue of 15-deoxyspergualin, an antibiotic used as an immunosuppressive agent to prevent rejection of organ transplants. Anisperimus enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC level. Phase I clinical studies were being conducted by Fournier in France for Transplant rejection and Phase II clinical studies for Autoimmune disorders in Europe. However development of anisperimus has been discontinued.

Tresperimus is a new stable immunosuppressive analog of 15-deoxyspergualin (DSG) obtained by organic chemical synthesis. It was initially developed as an antitumor agent. Tresperimus has been designed to be chemically stable in aqueous solution. Tresperimus controlled alloreactivity in a fully major histocompatibility complex (MHC) mismatched rat cardiac transplant model and also induced donor-specific long-lasting unresponsiveness. Posttransplant tresperimus therapy effectively protected mice from lethal graft-versus-host disease (GVHD) in a dose-related manner. It has been shown to suppress graft rejection as efficiently as cyclosporine A. Indeed, a short course of tresperimus has similar or better effects compared to the effects of cyclosporine in bone marrow, cardiac, and skin transplant models. Prevention of rejection is related to the induction of donor-specific tolerance without affecting immunity to third-party antigens. In addition, CD4+ T-cells from tresperimus-treated animals can transfer donorspecific tolerance to naive animals, an effect not seen with cyclosporine or other traditional immunosuppressive drugs. The mechanism by which tolerance is induced is not clear. Tresperimus binds to Hsc70, a heat shock protein– chaperoned peptide that, among other effects, inhibits nuclear localization of nuclear factor (NF)-kB, which is required for CD40 and CD28 ligation signaling in antigen-presenting cells, an important early step in T-cell costimulation. Locally administered tresperimus appears to be a potential immunosuppressive agent in the management of intraocular inflammation. Tresperimus had been in phase III clinical trial for the treatment of graft-versus-host disease. However, this development was discontinued.