Tetrahydropalmatine is a tetrahydroprotoberberine isoquinoline alkaloid that is a primary active constituent of herbal preparations containing plant species of the genera Stephania and Corydalis. The levo isomer of THP (L-THP) appears to contribute to many of the therapeutic effects of these preparations. The pharmacological profile of L-THP, which includes antagonism of dopamine D1 and D2 receptors and actions at dopamine D3, suggests that it may have utility for treating addiction. Clinical trials where L-THP was used for the treatment of cocaine and heroin addiction have promising results. The clinical trial is planned for the treatment of schizophrenia. L-Tetrahydropalmatine is recorded in the Chinese pharmacopoeia.

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

FLORTAUCIPIR is a gamma-carboline derivative. Its 18F radiolabelled form is a highly selective positron emission tomography (PET) tracer targeting paired helical filament (PHF)-tau in the brain. This tracer is studying for clinical assessment in patients with various tauopathies, including Alzheimer's disease.

Esuberaprost (314d) is an active enantiomer of beraprost, a prostacyclin analog. The pharmacologic action of esuberaprost is mediated by specifically binding to PGI2 receptors in smooth muscle cells (the blood vessel’s endothelium) and platelets. Upon binding, the compound widened blood vessels, preventing the formation of blood clots, and lowering blood pressure in the lungs. As a result, it was expected to improve the symptoms of pulmonary arterial hypertension. United Therapeutics announced it has ended its Phase 3 BEAT trial testing esuberaprost as an add-on therapy to its product Tyvaso (inhaled treprostinil) for clinically symptomatic patients with pulmonary arterial hypertension (PAH). According to a company press release, the study failed to reach its main endpoint of delaying the time to first clinical worsening events.

Dibrospidium (Spyrobromin) is a dispirotripiperazine derivative and alkylating agent with potential antineoplastic and anti-inflammatory activities. The duration of DNA synthesis inhibition in tumor cells was found to correlate with spirobromine antitumor activity. Spirobromin is superior to prospidin by the power of the anti-inflammatory effect. Spyrobromin can diminish the latent period of the development of tumours in the experimental rats at intraperitoneal administration. At intragastric administration of the drug no decrease was noted in the latent period and no increase of tumours was observed in the experimental groups of the animals as compared with control. Dibrospidium has been examined for the treatment of bone cancer. The oral route of administration is the most safe with respect to the oncogenic risk. It was noted that spirobromin exerted the most pronounced toxic action on erythrocytes. Dibrospidium is used for the treatment of acute leukemias (mainly in combination therapy), malignant lymphomas, laryngeal cancer and skin reticulosis.

Sapacitabine (also known as CYC-682) is an orally bioavailable 2′-deoxycytidine analog that is in clinical trials for hematologic malignancies and solid tumors. Sapacitabine is primarily metabolized by plasma, gut and liver amidases into the active metabolite CNDAC. This metabolite is subsequently transported inside cells and then phosphorylated by deoxycytidine kinase (dCK) into CNDAC triphosphate before being incorporated into cellular DNA. Sapacitabine participated in phase III clinical in older patients with acute myeloid leukemia (AML); however, it failed to meet its primary endpoint of the statistically significant improvement in overall survival (OS). The drug has been also involved in phase II clinical trials for the treatment of patients with myelodysplastic syndromes, cutaneous T-cell lymphoma, and non-small cell lung cancer. In addition, in combination with olaparib the drug was studied in phase I/II trial as a possible treatment for breast cancer with a BRCA mutation. On July 1, 2010, Cyclacel Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to the company’s sapacitabine for the treatment of both acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS).

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.