Vidupiprant, also known as AMG 853, is an orally bioavailable and potent dual antagonist of the D-prostanoid and chemoattractant receptor-homologous molecule expressed on T helper 2 cells receptors. Vidupiprant inhibits PGD2-induced down modulation of CRTH2 on CD16- granulocytes in human whole blood as well as PGD2-induced cAMP response in platelets. It inhibits PGD2-induced airway constriction in vivo. Also inhibits BRD4 (Kd = 170 nM). AMG 853 as an add-on to inhaled corticosteroid therapy demonstrated no associated risks but was not effective at improving asthma symptoms or lung function in patients with inadequately controlled moderate-to-severe asthma. AMG 853 has been discontinued due to poor efficacy.

Reparixin is a CXC chemokine receptor type 1 (CXCR1) and type 2 (CXCR2) inhibitor. This compound has potential antineoplastic activity. It can be administered orally, binds to CXCR1 (overexpressed on cancer stem cells) and prevents its activation by its ligand interleukin 8. This might result in the death of cancer cells and inhibition of cell progression and metastasis. Reparixin also inhibits CXCR2 activation, possibly reducing both neutrophil recruitment and vascular permeability during inflammation or injury. A phase II clinical trial evaluating the effects of orally administered reparixin on cancer stem cells in the primary tumor and the tumoral microenvironment in an early breast cancer population was terminated. Reparixin has also been suggested as a novel potential therapeutic strategy for aggressive forms of thyroid cancer, based on results of a xenotransplantation study in mice.

Firategrast (SB683699) is an orally bioavailable alpha4 beta1/alpha4 beta7 integrin antagonist designed to reduce trafficking of lymphocytes into the central nervous system (CNS), that had been studied in phase II trials at GlaxoSmithKline under a license from Mitsubishi Tanabe Pharma for the oral treatment of multiple sclerosis (MS) in Europe. GlaxoSmithKline and Tanabe Seiyaku (now Mitsubishi Tanabe Pharma) had been studying the drug candidate for the treatment of asthma, rheumatoid arthritis (RA) and Crohn’s disease, but these studies had being discontinued. Firategrast is a drug for the treatment of multiple sclerosis (MS) which is found to be caused by the migration of leucocytes (such as monocytes, T cells, B cells and dendritic cells) into CNS. And the integrin α4β1 is found to take participate in the migration through activating the leucocytes. Firategrast has a much shorter half-life than natalizumab with about 2.5 hours to 4.5 hours. It is found to inhibit the binding of the integrins to the associated ligands, including vascular cell adhesion protein 1 and mucosal addressin cell adhesion molecule 1. In CNS, firategrast treatment caused moderate decreases of total lymphocyte count, lymphocyte subset count and the ratio of CD4 to CD8. In peripheral blood, firategrast treatment resulted in the increases of total lymphocyte count, all lymphocyte subset count as well as the peripheral CD34+ early haematopoietic progenitor cell count. Firategrast was well tolerated at the maximum doses of 1200 mg for men and 900 mg for women. Firategrast showed no side effects, such as PML or JC-virus reactivation, at these doses. In Phase I clinical trials, the administration of firategrast significantly reduced the cumulative number of new gadolinium-enhancing lesions in patients with relapsing remitting MS.

Spirogermanium [NSC 192965, Spiro-32] is a germanium derivative which was under development by Unimed Pharmaceuticals. Spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being the most susceptible to this agent. Activity in malignant lymphoma, ovarian cancer, breast cancer, large bowel cancer, and prostatic cancer was reported in the clinical studies. The drug was under clinical investigation against the wide spectrum of solid tumors and malignant lymphomas. Spirogermanium also exhibits antiarthritic and immunoregulatory activities after p.o. administration to rats. Spirogermanium decreased hindleg inflammatory lesions of adjuvant arthritic rats when administered p.o. before or after the development of the arthritic lesions. However, the therapeutic use of spirogermanium has been discontinued because of its high toxicity and the low response rate.

Piclopastine is an antihistamine agent.

Ruclosporin is a calcineurin inhibitor that was developed as an immunosuppressant. Information about the further development of this compound is not available.

Delmitide is the decapeptide with antiinflammatory activity. It is the first low molecular weight compound inhibiting TNF production at a translational level. Also, delmitide inhibits production of IFN-gamma, IL-12 and IL-2. It targets TRAF6/IRAK4/MyD88 complex and inhibits phosphorylation of SAPKs (p38 and JNK). Delmitide inhibits AP1 and NFkB activation. Delmitide was developed for the potential treatment of Crohn's disease and ulcerative colitis; phase II trials for both these indications commenced in October 2001. Phase I trial in chemotherapy-induced diarrhea and the gastrointestinal complications of HIV were also initiated. However, no recent development has been reported.

Edratide (hCDR1 or TV-4710) is a peptide based on the sequences of the complementarity determining region (CDR) 1 of monoclonal anti-DNA antibody. The capacity of the peptide to bind to major histocompatibility complex class II molecules correlated with the proliferative responses. Edratide is being developed for the treatment of SLE (Systemic Lupus Erythematosus). Edratide ameliorates the SLE-related autoimmune process by specific upstream immunomodulation through the generation of regulatory T cells.

Oxeclosporin (previously known as SDZ IMM 125 and now called as tigderimus) was developed as an immunosuppressive drug. It was shown that the drug possessed apoptotic activity via induction of uptake of extracellular calcium. The increased intracellular calcium might directly cause apoptosis by increasing the caspase-3 activity. Oxeclosporin was studied in clinical trials in patients with severe psoriasis. In addition, it was used for the treatment of rheumatoid arthritis and transplant rejection. However, all these studies were discontinued. Besides, oxeclosporin is participating in phase II trials in Europe for the treatment of asthma and in Switzerland for the treatment of cancer. However, information about the further development of this drug is not available.