MGL-3196 is a first-in-class, orally administered, small-molecule, liver-directed, THR β-selective agonist. Preclinical, toxicology and Phase 1 clinical data suggest MGL-3196 has an attractive, differentiated profile as a potential treatment for non-alcoholic steatohepatitis (NASH) and dyslipidemias. THR-β selectivity also enhances the safety profile of MGL-3196, compared to non-selective agents. MGL-3196 has shown no suppression of the central thyroid axis, no THR-α effects on heart rate or bone, and no elevation of liver enzymes. These characteristics make MGL-3196 among the most promising molecules in development in this therapeutic area. MGL-3196 is in a Phase 2 clinical trial for the treatment of non-alcoholic steatohepatitis (NASH).

Vorasidenib (also known as AG 881) was developed as an isocitrate dehydrogenase (IDH) type 1 in the cytoplasm and type 2 in the mitochondria, with potential antineoplastic activity. It is known that IDH is an essential enzyme for cellular respiration in the tricarboxylic acid (TCA) cycle. Isocitrate dehydrogenases 1 and 2 (IDH1/2) are homodimeric enzymes that catalyze the conversion of isocitrate to α-ketoglutarate (α-KG) in the tricarboxylic acid cycle. Vorasidenib participated in phase I clinical trials in patients with advanced hematologic malignancies and in gliomas.

Flurpiridaz F-18, a fluorine 18-labeled agent was developed by Lantheus Medical Imaging for the diagnosis of coronary artery disease (CAD), the most common form of heart disease, which affects an estimated 15.5 million Americans 20 years of age or older. Flurpiridaz F 18 is an investigational positron emission tomography (PET) myocardial perfusion imaging (MPI) agent. GE Healthcare has launched a second Phase III clinical trial for the use of Flurpiridaz 18F Injection in PET myocardial perfusion imaging (MPI) to detect CAD.

Elafibranor (GFT505) is an agonist of the peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-δ. GFT505 has an active metabolite, GFT1007, and both have potent agonist activity for PPAR-a and to a lesser extent for PPAR-d. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. Elafibranor (GFT505) reverses nonalcoholic steatohepatitis (NASH) to prevent fibrosis progression. With an outstanding safety and tolerance profile, elafibranor provides NASH patients with needed cardio-protective benefits. Elafibranor is currently being evaluated in the clinical Phase 3 study RESOLVE-IT. The safety profile of GFT505 from the completed clinical trials appears satisfactory with no indication of PPAR-g agonist effects such as edema or body weight gain.

Arimoclomol citrate is an experimental drug developed by a biopharmaceutical company CytRx Corporation. In 2011 the worldwide rights to arimoclomol were bought by Danish biotech company Orphazyme ApS. The European Medicines Agency (EMA) and U.S. Food & Drug Administration (FDA) granted orphan drug designation to arimoclomol as a potential treatment for Niemann-Pick type C in 2014 and 2015 respectively. Arimoclomol is believed to function by stimulating a normal cellular protein repair pathway through the activation of molecular chaperones. Since damaged proteins, called aggregates, are thought to play a role in many diseases, CytRx believes that arimoclomol could treat a broad range of diseases.

Landiolol (Onoact) is an intravenously administered, ultra short-acting β1-blocker with an elimination half-life of 3-4 min and ≈8-fold greater cardioselectivity than esmolol in vitro. It is approved in Japan for the treatment of intraoperative and postoperative tachyarrhythmias, but in clinical practice is also used to prevent postoperative tachyarrhythmias, such as atrial fibrillation after coronary artery bypass grafting. Randomized controlled trials in patients undergoing open-heart surgery demonstrated that various dosages of landiolol (0.0005-0.04 mg/kg/min) [0.5-40 μg/kg/min] were more effective than diltiazem in converting postoperative atrial fibrillation to normal sinus rhythm during the first 8 h after surgery, and were more effective than placebo (or no landiolol) in preventing the development of atrial fibrillation during the first week after surgery (primary efficacy endpoints). Landiolol was generally well tolerated in clinical trials, with a relatively low risk of hypotension and bradycardia, although routine monitoring of cardiac function during landiolol administration is important. In general, adverse events such as reduced blood pressure resolve quickly after discontinuation of landiolol. Thus, as an ultra short-acting β1-blocker with a rapid onset of action and readily titratable and rapidly reversible effects, landiolol represents an important agent for the management of intraoperative and postoperative tachyarrhythmias.

Vadadustat is an Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitor. Patients with chronic kidney disease (CKD) have reduced levels of erythropoietin (EPO) and iron in the body, which can result in decreased number of oxygen-carrying red blood cells (RBCs) (anemia). The deficiency in RBCs causes inadequate oxygen delivery to cells and tissues. Vadadustat simulates the hypoxia response pathway by stabilizing key regulatory proteins called HIFs. Under normal conditions, when sufficient oxygen is present, HIF proteins are targeted for degradation by HIF-PH to maintain homeostasis in RBC production. Under conditions of hypoxia, HIF-PH activity is reduced, resulting in HIF stabilization. Stable HIF moves to the nucleus, where it activates target genes that increase EPO synthesis, resulting in the production of new RBCs, and suppression of hepcidin to promote iron absorption and mobilization. Vadadustat is currently in the phase 3 stage of development for the treatment of anemia secondary to CKD.

MBX-8025 (Seladelpar) is an agonist of peroxisome proliferator-activated receptor delta. MBX-8025 improves insulin sensitivity and reverses dyslipidemia and hepatic storage of lipotoxic lipids to improve nonalcoholic steatohepatitis pathology in atherogenic diet-fed obese diabetic mice. MBX-8025 improves lipoprotein subfractions associated with atherogenic dyslipidemia. CymaBay Therapeutics is developing MBX-8025 for the treatment of patients with the autoimmune liver disease, primary biliary cholangitis and nonalcoholic steatohepatitis.

AMD-070 is a small molecule drug candidate that belongs to a new investigational class of anti-HIV drugs known as entry (fusion) inhibitors. Approximately 76% of HIV-patients with measurable viral load are infected with a strain of virus that is resistant to one or more classes of antiretroviral agents, thus reducing treatment options. Unlike many existing HIV drugs that target the virus after it has infected a healthy cell, AMD-070 blocks the virus from entering a healthy cell, thus preventing the replication process. AMD-070 targets the CXCR4 receptor on HIV and prevents the virus from entering and infecting healthy cells. AMD-070 is specific for the CXCR4 receptor and does not interact with any other chemokine receptors in vitro. AMD-070 strongly inhibits viral infection by all CXCR4 using virus (including virus using CXCR4 alone and/or virus using CXCR4 and CCR5) in vitro. AMD-070 is orally bioavailable in animals, it has suitable PK and toxicity profile for oral dosing. AMD-070 shows additive or synergistic effects in vitro in combination with other known anti-HIV agents. AMD-070 is active against CXCR4 using HIV strains that are resistant to existing antiretroviral therapies in vitro, reveals potent anti-HIV activity against CXCR4-using laboratory strains and clinical isolates. MD-070 had been in phase II clinical trials by Genzyme for the treatment of HIV infection. However, this research has been discontinued. AMD-070 has been studied in Phase I/II clinical trials for the treatment of Renal cell carcinoma and Phase I clinical trials for the treatment of malignant melanoma and solid tumours.