Voruciclib (also known as P1446A-05) is a flavone-based, potent and selective CDK 4/6 inhibitor with activity in multiple BRAF-mutant and wild type cell lines. It is currently in clinical trials in combination with BRAF inhibitor (PLX4032) to treat advanced BRAF-mutant melanoma. Voruciclib has significant inhibitory activity against cutaneous and uveal melanoma. Mechanistic studies revealed that P1446A-05 inhibits phosphorylation targets of CDK members, and induces cell cycle arrest and apoptosis irrespective of melanoma genotype or phenotype. Voruciclib Hydrochloride is in phase I clinical trials by Piramal Life Sciences for the treatment of chronic lymphocytic leukaemia and malignant melanoma.

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.

Aftobetin, also known as ANCA11 and NCE-11, is a novel amyloid–binding compound applied topically in the form of an ophthalmic ointment. Aftobetin offers a promising way for a noninvasive eye-scan to diagnose Alzheimer’s disease early.

Revexepride is a selective 5-hydroxytryptamine receptor 4 agonist and member of a class of prokinetic agents that stimulate gastric emptying. Revexepride is thought to stimulate the release of acetylcholine at the myenteric plexus, leading to increased gastrointestinal contractions. This drug has been evaluated for potential use in treatment of gastroesophageal reflux disease. Phase I studies in healthy volunteers have shown no serious adverse events after administration of revexepride. However, a phase II study reported respiratory, thoracic and mediastinal disorders and pulmonary hypertension in 1 patient (0.85%). Furthermore, a European clinical trial showed that four weeks of treatment did not improve symptoms or gastric emptying in patients with symptoms suggestive of gastroparesis compared to placebo.

24-Hydroxycalcidiol (24,25-dihydroxy vitamin D3) is a circulating metabolite of vitamin D3. 24,25(OH)2D3 functions by activation of Vitamin D receprtor and promotion of ostecalcin expression, but is less effective than other D3 metabolite, 1alpha,25(OH)2D3. There is conflicting evidence on efffect of 24-hydroxycalcidiol on bone metabolism. In several animal studies it was demonstrated that 24-hydroxycalcidiol was able to stimulate calcification of bone and restore the reduction in bone mineral apposition rate. However, no beneficial effect of 24R,25(OH)2D3 treatment of postmenapausal women on bone mineral density or bone loss and calcium metabolism were observed.

NS-3728 (Endovion) is an orally active chloride channel blocker for the treatment of cancer. Endovion was originally discovered by NeuroSearch. In August 2004, NeuroSearch entered into a collaboration with TopoTarget to develop its compound Endovion, an orally active chloride channel blocker for the treatment of cancer. Endovion blocks a certain subtype of chloride ion channels important for cell division, cell migration and the formation of new blood vessels (angiogenesis). Endovion has shown efficacy in preclinical cancer models. The compound has completed Phase I clinical trials in 92 subjects. Endovion had been in phase I clinical trials for the treatment of sickle cell anemia and solid tumours. TopoTarget has discontinued development of Endovion for use in glioblastoma. It was discontinued as supplementary preclinical trials did not support its activity as an anticancer agent. Early studies as an anti sickling agent were discontinued due to higher costs than first estimated for the clinical programme.

Malethamer is the generic name of a new synthetic hydrocarbon copolymer with extraordinary water-binding properties, being able to absorb 200 times its weight of water. It is physically and chemically binds poliovirus 1 and certain bacterial enterotoxins. Ethylene-maleic anhydride copolymers and their derivatives have come to be considered for a number of applications generally involving the formation of insoluble complexes with proteins and viruses. The copolymer is not absorbed from the gastrointestinal tract and is pharmacologically inert. Malethamer, because of its water absorbing quality, is an effective compound for the symptomatic control of diarrhea, both organic and functional.