LMI-070 is an experimental compound being developed by Novartis Pharma as a treatment for spinal muscular atrophy (SMA). It is a small-molecule drug which modifies alternative splicing of the SMN2 gene, bringing about increased levels of SMN protein. LMI-070 originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multiparameter lead optimization. In a severe mouse SMA model, LMI-070 treatment increased full-length SMN RNA and protein levels, and extended survival. LMI-070 is taken orally, usually in a liquid form once a week. It is in phase II clinical trial.

Entospletinib (GS-9973) is an adenosine triphosphate competitive inhibitor of Syk that disrupts kinase activity, which is currently in clinical trials for multiple B-cell malignancies. The most common treatment-emergent serious adverse events included dyspnea, pneumonia, febrile neutropenia, dehydration, and pyrexia.

Antroquinonol is isolated from Antrodia camphorata, a camphor tree mushroom, and is a valuable traditional Chinese herbal medicine that exhibits pharmacological activities against several diseases, including cancer. Antroquinonol displayed anticancer activity against hepatocellular carcinoma cell lines through activation of 5′ adenosine-monophosphate-activated protein kinase and inhibition of the mammalian target of rapamycin (mTOR) pathway. Antroquinonol also exhibits anticancer activity in human pancreatic cancers through inhibition of the phosphoinositide-3 kinase (PI3K)/Akt/mTOR pathway, which in turn downregulates the expression of cell cycle regulators. The translational inhibition causes a G1 arrest of the cell cycle and ultimately mitochondria-dependent apoptosis. A study on the A549 pulmonary adenocarcinoma cell line demonstrated that antroquinonol-induced apoptosis was associated with disrupted mitochondrial membrane potential and activation of caspase-3 and poly ADP ribose polymerase cleavage. Moreover, antroquinonol treatment downregulated the expression of B-cell lymphoma 2 proteins, which was correlated with decreased PI3K and mTOR protein levels, without altering the levels of pro- or antiapoptotic proteins. Antroquinonol is currently in phase II trials (USA and Taiwan) for the treatment of non-small-cell lung carcinoma (NSCLC), atopic dermatitis; colorectal cancer; hepatitis B; hyperlipidaemia; pancreatic cancer. Antroquinonol was also approved for drug clinical trials by the Russian Ministry of Health (MoH). The MoH gave permission to test the efficacy and safety of Phase II clinical trials in patients with acute myeloid leukemia in Russia. Antroquinonol received the Orphan Drug Designation by the FDA in treatment of pancreatic cancer, liver cancer and acute myeloid leukaemia.

Idasanutlin (RG-7388) is a second-generation, orally bioavailable, selective p53-MDM2 antagonist. MDM2 is an important negative regulator of the p 53 tumor suppressor and is expressed at high levels in a large proportion of acute myeloid leukemia (AML). Blocking the MDM2-p53 interaction stabilizes p53 and activates p-53 mediated cell death and inhibition cell growth. Idasanutlin is under clinical trial in phase III for treatment AML and in combinations with others drugs in phase I/II for treatment of multiple myeloma.

Ralinepag is a cyclohexyl amide derivative patented by Arena Pharmaceuticals, Inc. as agonists of the human prostacyclin (PGI2) receptor useful for the treatment of pulmonary arterial hypertension. Ralinepag shows selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30-50-fold selectivity over the EP3 receptor. Ralinepag had an excellent PK profile across species. Enterohepatic recirculation most probably contributes to a concentration-time profile after oral administration in the cynomolgus monkey that showed a very low peak-to-trough ratio. Phase III clinical trial is currently ongoing.

Seletalisib (UCB-5857) is a potent, ATP-competitive, and selective phosphoinositide 3-kinase (PI3K) delta inhibitor. Findings from cellular assays of adaptive immunity demonstrated that seletalisib blocks human T-cell production of several cytokines from activated T-cells. Additionally, seletalisib inhibited B-cell proliferation and cytokine release. In human whole blood assays, seletalisib inhibited CD69 expression upon B-cell activation and anti-IgE-mediated basophil degranulation. Seletalisib safety, tolerability and pharmacokinetic/pharmacodynamic profiles support its continued clinical development in immune-inflammatory diseases. UCB Pharma is developing Seletalisib for the treatment of immune and inflammatory diseases including Activated PI3K delta Syndrome (APDS), Sjogren's syndrome and psoriasis.

Bryostatin 1 is a macrocyclic lactone which can be isolated from the marine bryozoan, Bugula neritina. The effects of bryostatin 1 are attributed to its ability to selectively modulate the activity of two of the three subgroups of protein kinase C (PKC) isozymes. PKC isozymes are divided into three subgroups which differ in their molecular structures and co-factor requirements: classical PKC (cPKC), novel PKC (nPKC), and atypical PKC (aPKC). Bryostatin-1 modulates nPKC activity independent of a Ca2+ signaling. It activates cPKC only when associated with Ca2+ signaling. And, aPKC activity is not sensitive to bryostatin-1 administration. Ca2+ signals play an important role in synaptic transmission and information processing which creates a biological environment where Bryostatin-1 possesses a unique action profile. Bryostatin-1 will not affect cPKC activity in neurons which are not functioning as an active part of the signaling processing circuit with significant Ca2+influx and intracellular Ca2+ release. Bryostatin 1 is in phase II clinical trials for investigation as an anticancer agent; specifically for treatment of metastatic or recurrent head and neck cancer, ovarian epithelial cancer that has not responded to previous chemotherapy, and myelodysplastic syndrome. Bryostatin 1 has also generated interest as an investigational compound for the treatment of Alzheimer's disease.

Cannabidivarin is a homolog of cannabidiol, with a well-established antiepileptiform profile in preclinical studies, both in vitro and in vivo animal models of epilepsy. The oral bioavailability of cannabidivarin is very low (about 6%) due to erratic absorption and first pass metabolism. After oral administration, the maximum plasma concentration of Cannabidivarin is rising in about three hours and the drug has a large volume of distribution, because of his link to protein plasma, being highly liposoluble, so CBDV can penetrate well to the brain. Cannabidivarin is also metabolized in the liver to 7-COOH and 6-OH metabolites, but the mechanism is also unknown. There is an ongoing phase II double-blind, placebo-controlled trial that is assessing the efficacy and safety of cannabidivarin in Children With Autism Spectrum Disorder (ASD).