Calanolide A is a new non-nucleoside reverse transcriptase inhibitor (NNRTI) originally extracted from a tropical tree (Calophyllum lanigerum) in the Malaysian rain forest. Viral life-cycle studies indicate that calanolide A acts early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor 2', 3'-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibits recombinant HIV type 1 RT but not cellular DNA polymerases or HIV type 2 RT within the concentration range tested. Phase I studies have found that calanolide A is well tolerated. Consequently, it has potential clinical applications in combination with other antiviral drugs to suppress HIV-1 mutants. Nevertheless, the development of calanolide A has been delayed due to its low therapeutic index (range: 16–279), non-ideal antiviral activity, and the complexity of its extraction from plants

GlaxoSmithKline is developing GSK-356278 as a selective, brain-penetrant phosphodiesterase 4 (PDE4) inhibitor that demonstrates anxiolytic and cognition-enhancing effects. Small molecule phosphodiesterase (PDE) 4 inhibitors have long been known to show therapeutic benefit in various preclinical models of psychiatric and neurologic diseases because of their ability to elevate cAMP in various cell types of the central nervous system. The drug was studied for the treatment of Huntington's disease, depressive and anxiety disorders. GSK-356278 has completed phase I clinical trials for evaluation of the safety, tolerability, and pharmacokinetics in male volunteers with the therapeutic dose for future clinical development.

Dideoxyadenosine (2′,3′-dideoxyadenosine) is a prodrug form of didanosine (2',3'-dideoxyinosine), a nucleoside reverse transcriptase inhibitor analog of adenosine. 2',3'-Dideoxyadenosine and 2',3'-dideoxyinosine were shown to be equally effective in the inhibition of HIV proliferation in human T cells. Dideoxyadenosine competitively inhibits adenylyl cyclase, thereby reducing levels of cyclic adenosine monophosphate (cAMP). By inhibiting cAMP-mediated gene activation in tumor cells, this agent may retard tumor cell proliferation. 2',3'-dideoxyadenosine inhibits retroviral DNA synthesis and mRNA expression in T cells exposed to the virus that causes acquired immunodeficiency syndrome, and affords such cells long-term protection in vitro under conditions of substantial viral excess. 2',3'-dideoxyadenosine appears to completely block reverse transcription from viral RNA to viral DNA. 2',3'-dideoxyadenosine was also shown not only to possess antibacterial activity in vitro against a variety of Enterobacteriaceae, but also to be effective in vivo, dideoxyadenosine was active in experimental mouse infections by the oral route against 5 Salmonella strains, 2 of 3 Arizona strains, 5 of 7 Citrobacter strains, 3 of 8 Klebsiella strains, 3 of 5 Escherichia strains, 1 of 3 Shigella strains, and 3 of 15 Serratia strains at concentrations generally well below the toxic level.

LY2452473 is a selective androgen receptor modulator (SARM), with potential tissue-selective androgenic/anti-androgenic activity. Upon oral administration, LY2452473 acts as an agonist in select tissues and organs, including skeletal muscle, bone and the penis, thereby binding to and activating androgen receptor (AR) while acting as an antagonist in the prostate, thereby blocking AR activation and AR-mediated cellular proliferation. This may improve muscle mass and strength, bone formation, and erectile dysfunction while not stimulating growth of the prostate. Eli Lilly was developing LY 2452473/tadalafil combination for the treatment of erectile dysfunction. In addition, Eli Lilly is studying the use of a targeted LY 2452473 therapy, as a possible improvement in quality of life for prostate cancer patients who have undergone radical prostatectomy.

Friulimicin B (or friulimicin) is a naturally occurring antibiotic produced by a microorganism Actinoplanes friuliensis. This drug is active against a broad spectrum of gram-positive multi drug resistant, invasive pathogens. Friulimicin B participated in phase I clinical trials provided by MerLion Pharmaceuticals for the treatment of nosocomial infections. However, information about the further development of this drug is not available.

Tandamine was developed as a selective serotonin reuptake inhibitor for the treatment of depression. Tandamine participated in clinical trials in hospitalized depressed patients, where it showed that the well-tolerated drug could be of some benefit for retarded depressions. In addition, was found in human volunteers, that tandamine possessed significant anticholinergic activity, to reduce appetite and to produce sedation. However, this drug has never been marketed.

Diazepinomicin is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. A small-molecule inhibitor of the RAS/RAF/MAPK signaling pathway with potential antineoplastic activity. Diazepinomicin binds to and inhibits Ras kinase, thereby preventing the phosphorylation and activation of proteins downstream of the Ras signal transduction pathway, including serine/threonine kinase RAF (BRAF) and extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK-2). This agent also selectively binds to the peripheral benzodiazepine receptor (PBR), a receptor highly expressed in certain tumor cell types, inducing cell cycle arrest and apoptosis in PBR-expressing cells. The compound was shown to have a broad cytotoxic activity in the low micromolar range, when tested in the NCI 60 cell line panel. Diazepinomicin can cross the blood-brain barrier. Diazepinomicin is in phase II clinical trials for the treatment of Telomeric 22q13 Monosomy Syndrome and phase I for the treatment of Fragile X syndrome.

Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of μ, δ, and κ opioid receptors. Norbuprenorphine is the only known active metabolite of buprenorphine. It has been shown to be a respiratory depressant in rats, but only at concentrations at least 50-fold greater than those observed following application to humans of BuTrans 20 mcg/h. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. In rats, nor-buprenorphine had 1/50th the analgesic potency of buprenor-phine but 10-fold greater respiratory depressant potency. Norbuprenorphine is an in vitro substrate of the efflux transporter P-glycoprotein (Mdr1). Norbuprenorphine is an in vitro and in vivo substrate of P-glycoprotein. P-glycoprotein-mediated efflux influences brain access and antinociceptive, but not the respiratory, effects of norbuprenorphine.

Borocaptate sodium B10 (also known as sodium borocaptate), a boron compound for use in boron neutron capture therapy. After parenteral administration, sodium borocaptate accumulates preferentially in tumor cells. When exposed to neutron irradiation, borocaptate absorbs neutrons and self-destructs releasing short-range alpha radiation and 'recoil' lithium in tumor cells, resulting in alpha radiation-induced tumor cell death. This highly selective, localized radio targeting of tumor cells, known as boron neutron capture therapy, spares adjacent normal tissues. Borocaptate sodium B10 was involved in phase I clinical trial in treating patients with glioblastoma multiforme removed during surgery to study the side effects. In addition, this compound participated in phase I clinical trials in tissues of patients with primary, metastatic, or recurrent thyroid cancer, head and neck cancer, or liver metastases from colorectal cancer to study the side effects. Besides, borocaptate sodium B10 was involved in phase-I clinical trials for Glioma in the European Union, however, this study was discontinued.