N-Gene Research Laboratories is developing BGP-15 (NP-51), a small molecule, orally available, indirect Jun kinase (JNK) inhibitor and insulin sensitiser, for glycaemic control in patients with type-2 diabetes mellitus, and as an adjunct treatment for insulin resistance due to antipsychotics or obesity. In March 2002, N-Gene Research Laboratories granted Allos Therapeutics an exclusive license to its intellectual property surrounding BGP 15 in the US. BGP-15 has previously been used in clinical trials for the treatment of skeletal muscle pathology associated with Type 2 Diabetes (through insulin sensitization), Duchenne Muscular Dystrophy (DMD) and heart failure (through anti-inflammatory and anti-fibrotic mechanisms). Via its action as a modulator of the cytoprotective response to cellularstress, and specifically as a poly (ADP-ribose) polymerase (PARP) inhibitor, heat shock protein-inducer, membrane lipid therapeutic and an antioxidant inducer, BGP-15 has previously been shown to protect against skeletal muscle dysfunction, damage and wasting.

KH-176 is a drug candidate developed by pharmaceutical company Khondrion to treat a range of mitochondrial diseases including MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) spectrum disorders. KH176 has been granted Orphan Drug Designation for MELAS spectrum disorders and Leigh disease in Europe and for all inherited mitochondrial respiratory chain disorders in the USA. KH176 acts as a potent intracellular redox-modulating agent essential for the control of oxidative and redox pathologies.

CC-122 is the first-in-class pleiotropic pathway modifiers that may work by binding cereblon and promoting the ubiquitination and the resulting degradation of the transcription factors Aiolos and Ikaros. It has been shown to have potent anti-proliferative, anti-angiogenic and immunomodulatory activities in B cell lymphoma, perhaps though its T and NK-cell activation and B-cell inhibition. CC-122 inhibits proliferation and induces apoptosis in a broad panel of diffuse large B-cell lymphoma cell lines, reduces tumor growth in xenograft models established from activated B-cell (ABC) and germinal center B-cell DLBCL cell lines, and stimulates IL-2 production in primary T cells. These activities are dependent on the binding of CC-122 to Cereblon and subsequent ubiquitination and proteasomal degradation of Aiolos and Ikaros, resulting in direct derepression of interferon (IFN)–stimulated gene (ISG) transcription and induction of IFN-inducible proteins, ultimately leading to apoptosis.

CH5183284/Debio 1347 is selective and orally available fibroblast growth factor receptors: FGFR1, FGFR2, and FGFR3 inhibitor that has a unique chemical scaffold. By interacting with unique residues in the ATP-binding site of FGFR1, FGFR2, or FGFR3, CH5183284/Debio 1347 selectively inhibits there receptors, but does not inhibit kinase insert domain receptor (KDR) or other kinases. CH5183284/Debio 1347 will provide therapeutic opportunities for patients who have FGFR genetic alterations and patients with acquired resistance to existing FGFR selective inhibitors that contain the common methoxy moieties.

Emixustat (formerly ACU-4429) is a nonretinoid compound with a unique mode of action in the retinal pigment epithelium, where it modulates the biosynthesis of visual chromophore through its effect on retinal pigment epithelium protein 65 (RPE65). Emixustat modulates the visual cycle by inhibiting a critical enzyme of this pathway RPE65. Acucela Inc., a Kubota Pharmaceutical company, is developing emixustat for the treatment of Stargardt disease and proliferative diabetic retinopathy.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

Dexpramipexole (also known as KNS-760704/R-pramipexole) was originally developed by University of Virginia researchers to treat Amyotrophic Lateral Sclerosis and then was licensed to global biotechnology company Biogen Idec for further development. However, on phase III clinical trial the study of this drug was discontinued. Biogen said the drug neither slowed the loss of muscle function nor prolonged the lives of patients with ALS, often called Lou Gehrig’s disease. Nor did it show any efficacy in secondary endpoints of the clinical trial, or work in any sub-group of patients—about a big a failure as a company could have a Phase III trial. In addition, was discovered, that dexpramipexole was able to bind to beta-subunit of the mitochondrial F1/FO ATP synthase complex and increased its activity, thus reduced ischemic brain injury. These findings, together with the excellent brain penetration and favorable safety profile in humans, make dexpramipexole a drug with realistic translational potential for the treatment of stroke.

ENMD-2076 is an orally-active, Aurora A/angiogenic kinase inhibitor. urora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers. ENMD-2076 also targets the VEGFR, Flt-3 and FGFR3 kinases, which have been shown to play important roles in the pathology of several cancers. ENMD-2076 is tested in phase 2 clinical trials against ovarian cancer, breast cance, hepatocellular carcinoma and other malignancies.

Sarizotan (also known as EMD-128,130), a chromane derivative that was developed as a selective 5-HT1A receptor agonist and D2 receptor antagonist. Experiments on animal models have shown that the drug effectively suppressed levodopa-induced dyskinesia in primate and rodent models of Parkinson's disease, and tardive dyskinesia in a rodent model. Sarizotan participated in phase II/III clinical trials in the treatment of dyskinesia associated with the dopaminergic treatment of Parkinson's disease. However, further development for this disease was discontinued by Merk, because phase III did not confirm earlier Phase II findings. On July 14, 2015, Newron Pharmaceuticals, research, and development company focused on the novel central nervous system (CNS) and pain therapies, announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to sarizotan for treatment of Rett syndrome. Besides, the drug now is an ongoing clinical trial phase II/III to investigate its the tolerability and efficacy in reducing respiratory abnormalities in Rett Syndrome.