Ricolinostat is a selective inhibitor of HDAC6 with IC50 value of 4.7 nM. Ricolinostat demonstrated good anti-proliferative activity on different cell lines and clinical models of cancer. The drug is being tested in phase I/II for the treatment of multiple myeloma and lymphoid malignancies and in phase I in patients with breast cancer, gynecological cancer, cholangiocarcinoma, recurrent chronic lymphoid leukemia.

Salvinorin A has been reported to be the most potent naturally occurring hallucinogen, with an effective dose in humans in the 200- to the 1,000-μg range when smoked; it has been reported to induce an intense hallucinatory experience in humans, with a typical duration of action being several minutes to an hour or so. Salvinorin A is a highly selective agonist of the kappa-opioid receptor (KOR) with few off-target effects. It is a potent and selective dilator of the cerebral vasculature, exhibits rapid penetration through the blood-brain barrier, has potent anti-inflammatory properties, and has the ability to preserve neurovascular unit integrity. As such, salvinorin A is an ideal compound for the prevention and treatment of cerebral vasospasm following subarachnoid hemorrhage.

Apabetalone (RVX-208) is a small molecule BET bromodomain inhibitor selective for BRD4-BD2 undergoing clinical development as a potential therapy to enhance ApoA-I production and treat atherosclerosis and prevent cardiovascular disease events. Apabetalone increases apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-Cholesterol) in vitro and in vivo which is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increased the Tm of all BET bromodomains, indicative of binding. RVX-208 competes for acetylated histone H4 peptide binding to both bromodomains of BRD4, similar to JQ-1, but with a preference for BD2 over BD1. RVX-208 also binds to the bromodomains of BRDs 2 and 3 with a similar preference for BD2 (Kd~5–30 nM) over BD1 (Kd~2–3 uM). Treatment of humans for 1 week with oral RVX-208 increased apoA-I, pre-beta-HDL, and HDL functionality. Resverlogix Corp. has commenced a Phase 3 clinical trial in cardiovascular disease patients with type 2 diabetes mellitus with a primary endpoint of time to first occurrence of Major Adverse Cardiac Events (MACE).

MIP-1095 I-123 is under investigation in clinical trial phase II to evaluate the safety and efficacy in combination with enzalutamide in patients with prostate-specific membrane antigen (PSMA)-avid metastatic castration-resistant prostate cancer who have progressed on abiraterone. It is known that MIP-1095 potently inhibited the glutamate carboxypeptidase activity of PSMA and when radiolabeled with 123I exhibited high affinity for prostate-specific membrane antigen (PSMA) on human prostate cancer LNCaP cells.

Licochalcone A (LicA) is a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch and has a wide spectrum of pharmacological activities such as anti-oxidant, anti-bacterial, anti-viral, and anti-cancer. However, its pharmacological mechanism is not well defined. The anti-Inflammatory effects of LicA on IL-1β-Stimulated human osteoarthritis chondrocytes was reached by activating Nrf2 signaling pathway. LicA showed anti-proliferative and apoptotic effects in breast cancer cells through regulating Sp1 and apoptosis-related proteins in a dose- and a time-dependent manner. In addition, the chemotherapeutic potential of LicA for treatment of human cervical cancer was achieved by inhibition of PI3K/Akt/mTOR signaling.

MK-0812 is a potent and selective CCR2 antagonist, which was developed by Merck. This drug has entered clinical trials for both rheumatoid arthritis and multiple sclerosis. However, the rheumatoid arthritis trial was terminated because of lack of favorable outcomes when MK-0812 failed to show any early clinical improvement. The outcome of the multiple sclerosis trial of MK-0812 also had negative outcomes.

Trabodenoson is a potent (Ki = 0.97 nM) and selective (>10,000- fold vs. adenosine 2 receptor) adenosine 1 receptor agonist. Ex vivo, trabodenoson (100 nM to 3 uM) progressively prolonged A-V-nodal conduction without reducing left ventricular function or coronary resistance. In vivo, trabodenoson up to a dose of 50 ug/kg did not reduce the carotid arterial blood pressure. Twice-daily ocular doses of trabodenoson, from 50 to 500 ug, were well tolerated and showed a dose-related decrease in intraocular pressure that was statistically significant and clinically relevant at 500 ug in patients with ocular hypertension or primary open-angle glaucoma. Trabodenoson had been in phase III clinical trial for the treatment of glaucoma and ocular hypertension. However, this development was discontinued.

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.

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.

MK-7145 is a piperazine derivative patented by Merck Sharp & Dohme Corporation as the renal outer medullary potassium channel inhibitor useful for the treatment of hypertension and heart failure. In preclinical studies, MK-7145 shows selectivity against other cardiac ion channels such as Cav1.2, Nav1.5, and Kir2.1, Kir2.3, Kir4.1, or Kir7.1. In 2011 MK-7145 was studied in phase I clinical trials but no further development reports were published.