Evacetrapib (LY2484595) is a novel benzazepine-based CETP inhibitor that has been developed at Lilly Research Laboratories. Evacetrapib inhibits CETP with IC50 of 5.5 nM, elevates HDL cholesterol without increases in aldosterone or blood pressure. Phase 3. On 01 Sep 2016 Eli Lilly terminates the phase III ACCENTUATE trial in Hyperlipidaemia (Adjunctive treatment) in USA and Puerto Rico (PO) due to insufficient efficacy (NCT02227784).

Oletimol was developed as an antirheumatic agent that has never been marketed. Information about the current use of this drug is not available.

Hydracarbazine, a diuretic, was used in France under the brand name Normatensyl as an antihypertensive drug.

Atiprosin (AY-28,228), an octahydro-pyrazino-pyrido-indole drug, possesses the alpha-adrenoceptor antagonist activity and exerts antihypertensive effects. Atiprosin has never been marketed

Tetrodotoxin (TTX) is a potent marine neurotoxin that blocks voltage-gated sodium channels (VGSCs). VGSCs play a critical role in neuronal function under both physiological and pathological conditions. TTX has been extensively used to functionally characterize VGSCs, which can be classified as TTX-sensitive or TTX-resistant channels according to their sensitivity to this toxin. Wex Pharmaceuticals is investigating tetrodotoxin for the treatment of chronic and breakthrough pain. The toxin is currently undergoing Phase III clinical trials in Canada as a systemic analgesic for inadequately controlled pain due to advanced cancer, especially where the pain has neuropathic features. In addition, TTX is in Phase II clinical trials to study its ability in moderate to severe neuropathic pain caused by chemotherapy.

Ammonium trichlorotellurate (AS-101) is a synthetic non-toxic tellurium derivative, structurally similar to cisplatin, with immunostimulatory and anti-hair loss properties. Ammonium trichlorotellurate induces production of colony stimulating factor (CSF), interleukin-2 (IL-2), and IL-2 receptors by increasing the calcium ion influx through the cell membrane and subsequently exerts its immunostimulatory effects through the CSF-mediated increase in macrophage/granulocytes. This agent is also a potent inducer of interferon and a spectrum of cytokines such as IL-1, IL-6, and tumor necrosis factor (TNF). In animal studies, ammonium trichlorotellurate exerts its anti-hair loss effect by inducing anagen and obstructing spontaneous catagen via promoting follicular keratinocyte proliferation and interfering with terminal differentiation, respectively. AS-101 suppresses production of HIV-1. It inhibited reverse transcriptase activity and replication of human immunodeficiency virus type 1. RDDP and DDDP activities were impaired by the drug with calculated IC50 value of about 4 uM. Intravenous AS-101 was in trials in patients with HIV infections. AS-101, a small-molecule integrin αvβ3 and VLA-4 inhibitor is being developed by BioMAS in Israel for the treatment of genital warts, age-related macular degeneration and fertility preservation. Phase II clinical trials are ongoing. The drug was also undergoing phase II development in acute myeloid leukaemia, atopic dermatitis, chemotherapy-induced damage, myelodysplastic syndromes, thrombocytopenia, alopecia, psoriasis. However, development for these indications was discontinued.

The monoterpene perillyl alcohol (POH) is a naturally occurring compound derived from citrus fruits, mint, and herbs. It exhibited chemotherapeutic potential against various malignant tumors in preclinical models and was being tested in clinical trials in patients with refractory advanced cancers. POH was formulated in soft gelatine capsules and orally administered to cancer patients several times a day on a continuous basis. However, such clinical trials in humans yielded disappointing results, also because of the large number of capsules that had to be swallowed caused hard-to-tolerate intestinal side effects, causing many patients to withdraw from treatment due to unrelenting nausea, fatigue, and vomiting. The clinical trials in Brazil have explored intranasal POH delivery as an alternative to circumvent the toxic limitations of oral administration. In these trials, patients with recurrent malignant gliomas were given comparatively small doses of POH via simple inhalation through the nose. Results from these studies showed, that this type of long-term, daily chemotherapy was well tolerated and effective. The precise mechanism of action is still undetermined, but it is known, that perillyl alcohol plays an important role in the process of hepatoma cell invasion and migration via decreasing the activity of Notch signaling pathway and increasing E-cadherin expression regulated by Snail. Another possible mechanism is included inhibition of Na/K-ATPase (NKA). The NKA α1 subunit is known to be superexpresses in glioblastoma cells (GBM) and POH acts in signaling cascades associated with NKA can control cell proliferation and/or cellular death.

Nanterinone [UK 61260], a phosphodiesterase III inhibitor, was undergoing II evaluation with Pfizer in the US for the treatment of heart failure. Nanterinone is a positive inotropic and balanced-type vasodilating drug, only partially based on phosphodiesterase III inhibition. Preliminary data from controlled studies suggest satisfactory long-term efficacy and safety.