Rimiducid (AP1903) is a lipid-permeable tacrolimus analogue with homodimerizing activity. Rimiducid homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val). This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered proteins such as the iCD40 receptor, Fas intracellular domain or iCaspase 9 resulting in downstream signaling activation during cell therapy. Orphan designation was granted for rimiducid (AP1903) for the treatment of graft-versus-host disease.

Deoxyspergualin is a derivative of the antitumor antibiotic spergualin, that used as an immunosuppressive drug. Deoxyspergualin shows immunosuppressive activity both in vitro and in vivo, affecting B-lymphocyte, T-lymphocyte and macrophage/monocyte function. In rodents and human cell systems, Deoxyspergualin shows a dose-dependent inhibition of primary and secondary responses to T-, B- and antigen-presenting cell-dependent reactions. Deoxyspergualin also blocks nuclear translocation of NF-kB in a pre-B-cell line, thereby affecting NF-kB driven transcription of the kappa light chain. Deoxyspergualin inhibits desoxyhypusine synthase, the first enzyme in the formation of active eukaryotic translation initiation factor 5A. This factor is important for the stabilization of certain mRNA transcripts (TNF-a and others). The immunosuppressive properties of Deoxyspergualin have been demonstrated in preclinical animal studies including Systemic lupus erythematosus models. In humans with glucocorticoidresistant kidney transplant rejection, Deoxyspergualin shows the same efficacy rate as the strongly T-cell depleting anti-CD3 monoclonal antibody. Deoxyspergualin has been licensed in Japan for acute renal allograft rejection since 1994. In 2003, an open clinical trial successfully tested Deoxyspergualin in patients with persistent ANCA-associated vasculitis. Adverse events (AE) were common but rarely led to treatment discontinuation. Against this background, Deoxyspergualin was granted an orphan drug status for the treatment of Wegener’s granulomatosis by the European Medicines Agency (EMA).

Pocapavir is a capsid-binding molecule. It is a capsid inhibitor that blocks virus uncoating and viral RNA release into cells, which in turn prevents virus replication. Pocapavir is a potent, selective, anti-enterovirus molecule with in vitro and in vivo activities. Antiviral testing against viruses of the 15 most commonly isolated enterovirus serotypes indicates that pocapavir inhibits 80% of the immunotypes (154 viruses) at a concentration that is within the levels of the molecule achievable in plasma after oral dosing in higher animals. Persistent low viral load after therapy completion may indicate lack of antiviral effect from pocapavir for neonatal enteroviral sepsis treatment. Pocapavir had been in phase II clinical trial for the treatment of poliomyelitis but no recent reports on development were identified.

17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235, Apoptone) is an orally bioavailable synthetic analogue of 3β-androstanediol, that is active in rodent models of prostate and breast cancer. HE3235 is a second generation antitumor agent that causes apoptosis. It is an androgen receptor antagonist. HE3235 inhibits the BCL2 gene which translates proteins that prevent apoptosis and stimulates the expression proteins that induce apoptosis. HE3235 also downregulates the gene that codes for the multi-drug resistant protein ABCG2 (BCRP1 – Breast Cancer Resistance Protein1). Apoptone was in Phase I/II trials to treat hormone-refractory prostate cancer. However, the development has been discontinued.

Aflatoxin B1 is a very potent carcinogen produced by Aspergillus flavus and related fungi that grow on improperly stored food such as corn, rice, and peanuts. Dietary exposure to aflatoxin B1 is associated with an increased incidence of hepatocellular carcinoma, especially given co-infection with hepatitis B virus. Mechanism of carcinogenicity involves metabolic activation to aflatoxin B1-8,9 exo-epoxide by cytochrome p450 and formation of adducts with guanine DNA base.

Patupilone is a compound isolated from the myxobacterium Sorangium cellulosum. Similar to paclitaxel, Patupilone induces microtubule polymerization and stabilizes microtubules against depolymerization conditions. In addition to promoting tubulin polymerization and stabilization of microtubules, this agent is cytotoxic for cells overexpressing P-glycoprotein, a characteristic that distinguishes it from the taxanes. Epothilone B may cause complete cell-cycle arrest. Patupilone failed a phase III trial for ovarian cancer in 2010.

GS-9190 (Tegobuvir) a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase was investigated for treatment Hepatitis C, Chronic, but on the clinical trial II was discontinued.

Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.

β-N-Acetyl-D-galactosamine (GalNAc) is an amino sugar derived from galactose found in O-linked and N-linked glycans. As an essential sugar, the role is basically the same for N-acetylgalactosamine as it is for the others, which is to enhance cellular communication. Although there has not been much research to date, what has been done reveals that this saccharide may inhibit the growth of some tumors. For example, colon cancer patients have only half the normal amounts of N-acetylgalactosamine. Studies have shown that colon cancer cells that metastasize make more mucin, making them more likely to form metastases. Therefore, it appears that N-acetylgalactosamine plays an important role in preventing this formation from occurring. N-acetylgalactosamine and N-acetylglucosamine glycans is a predictor of metastasis and poor prognosis in a number of human adenocarcinomas, including breast cancer. Lower than normal levels of this sugar has been found in patients with heart disease implying that these conditions may be reversed if a supplementation of N-acetylgalactosamine were to be added to the diet. It appears that β-N-Acetyl-D-galactosamine plays a role in joint function, sweeping away destructive free radicals that can cause inflammation. N-acetylgalactosamine also seems to play an important role in the immune system. Contained in macrophages and neutrophils, it may play a significant role in the etiology of joint inflammation and could be important in such conditions as rheumatoid arthritis. In humans, it is the terminal carbohydrate forming the antigen of blood group A. N-acetylgalactosamine (GalNAc) is a well-defined liver-targeted moiety benefiting from its high affinity with asialoglycoprotein receptor (ASGPR). By conjugating it directly to the oligonucleotides or decorating it to a certain delivery system as a targeting moiety, GalNAc has achieved compelling successes in the development of nucleic acid therapeutics in recent years. Several oligonucleotide modalities are undergoing pivotal clinical studies, followed by a blooming pipeline in the preclinical stage. N-Acetyl-D-galactosamine is used in affinity chromatography, protein chromatography and in carbohydrate matrices. N-Acetyl-D-galactosamine has been used to study periodontal disease and to facilitate the design of potent small-molecule ice recrystallization inhibitors. N-Acetyl-D-galactosamine has also been used to demonstrate a molecular shuttle between extracellular and cytoplasmic space allows for monitoring of GAG biosynthesis.