FGF-401 is an inhibitor of human fibroblast growth factor receptor 4 (FGFR4), with potential antineoplastic activity. Upon administration, FGF401 binds to and inhibits the activity of FGFR4, which leads to an inhibition of tumor cell proliferation in FGFR4-overexpressing cells. FGFR4 is a receptor tyrosine kinase upregulated in certain tumor cells and involved in tumor cell proliferation, differentiation, angiogenesis, and survival. FGF-401 is an FGFR4 inhibitor in phase I/II clinical studies at Novartis for the treatment of positive FGFR4 and KLB expression solid tumors and hepatocellular carcinoma.

Elacytarabine (CP-4055 or araC-5'elaidic acid ester) is a lipid-conjugated derivative of the nucleoside analog cytarabine. Elacytarabine blocks cell division and may kill cancer cells. It is a type of antimetabolite. It was studied in clinical trials for the treatment of solid tumors. In preclinical and clinical studies, elacytarabine has demonstrated both safety and efficacy in acute myeloid leukemia (AML), with noteworthy activity among the cytarabine-refractory AML population. Elacytarabine was granted orphan drug designation status from the European Commission in 2007 and from the US FDA in 2008, with a fast-track approval designation from the FDA in 2010. Elacytarabine development has been discontinued.

PF-06747775 is an irreversible pyrrolopyrimidine inhibitor of epidermal growth factor receptor (EGFR) T790M mutants which provides potent EGFR activity against the four common mutants (exon 19 deletion (Del), L858R, and double mutants T790M/L858R and T790M/Del), selectivity over wild-type EGFR, and desirable ADME properties. The third-generation class of EGFR tyrosine kinase inhibitors PF-06747775 is a clinical candidate drug for treatment of non-small-cell lung cancer (NSCLC) driven by mutant EGFR.

Icosabutate (also known as PRC-4016 or NST-4016), a cholesterol ester transfer protein inhibitor was developed by NorthSea Therapeutics for the treatment of combined dyslipidemias and hypertriglyceridemia. Icosabutate successfully completed phase II clinical trial for hypertriglyceridemic subjects, where was studied the drug efficacy and safety. In April 2018 NorthSea Therapeutics announced that its lead product, icosabutate would be further developed as an effective and safe therapeutic approach to treating both non-alcoholic steatohepatitis and its associated comorbidities.

2-(4,6-DIMETHYLPYRIMIDIN-2-YL)-5-((2-FLUORO-6-(2H-1,2,3-TRIAZOL-2-YL)PHENYL)CARBONYL)OCTAHYDROPYRROLO(3,4-C)PYRROLE (Seltorexant, MIN 202), a small molecule, selective orexin receptor type-2 antagonist, is being developed by Minerva Neurosciences and Janssen Research & Development for the treatment of insomnia and major depressive disorder. Seltorexant has shown high in vitro affinity (affinity pKi =8.0 and 6.1 for OX2R and OX1R respectively) for the human OX2R and approximates two logs selectivity ratio versus its affinity for the OX1R. Seltorexant demonstrated a dose-dependent normalization of sleep and a trend towards improvement of subjective depressive symptoms in antidepressant-treated MDD patients with residual insomnia. Additionally, seltorexant’s favorable PK profile as a potential sedative-hypnotic drug was confirmed in a MDD population and did not demonstrate unacceptable adverse events or unwanted next-day CNS effects. Seltorexant is in phase II clinical trials for both insomnia and MDD.

VLX600 - is a lipophilic cation-based triazinoindolyl-hydrazone compound and mitochondrial oxidative phosphorylation (OxPhos) inhibitor, with potential antineoplastic activity. VLX600 is designed to increase the efficacy of radiotherapy and to kill cancer cells that survive traditional chemotherapy. VLX 600 is a small molecule that inhibits deubiquitinating enzymes USP14 (a ubiquitin thiolesterase) and UCHL5 (a carboxypeptidase). Upon infusion, in normal cells and proliferating tumor cells where glucose is readily available, inhibition of OxPhos by VLX600 induces a hypoxia-inducible factor 1-alpha (HIF-1alpha)-dependent shift to, and an increase in glycolysis. Glycolysis alone does not produce enough energy to support the growth of tumor cells in this environment, and the induction of autophagy occurs. In the metabolically compromised tumor microenvironment, the availability of oxygen and glucose is limited due to poor vascularization and perfusion of tumor micro-areas. Tumor cells growing in this environment are thus unable to compensate for decreased mitochondrial function by increasing glycolysis. This leads to nutrient depletion, decreased energy production, induction of autophagy, tumor cell death and an inhibition of cell proliferation in quiescent tumor cells. Mitochondrial OxPhos, which is hyperactivated in cancer cells, plays a key role in the promotion of cancer cell proliferation. VLX-600 is in phase I clinical trials for the treatment of solid tumours. This compound was originally jointly discovered and developed by Vivolux and Karolinska Institute.

Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for the treatment of gout and asymptomatic hyperuricemia. Verinurad specifically inhibits URAT1 with a potency of 25 nM. High affinity inhibition of uric acid transport requires URAT1 residues Cys-32, Ser-35, Phe-365 and Ile-481. Unlike other available uricosuric agents, the requirement for Cys-32 is unique to verinurad. Verinurad doses as low as 2.5 mg produce significant sUA lowering in humans, and this greater reduction in sUA may lead to improved outcomes and medical benefits for patients with gout. Verinurad in monotherapy studies has been associated with increased urinary uric acid concentrations and low rates of serum creatinine (sCr) elevation. Verinurad combined with febuxostat decreased sUA dose-dependently while maintaining uric acid excretion similar to baseline. All dose combinations of verinurad and febuxostat were generally well tolerated.

Novartis Oncology (previously Novartis) is developing nazartinib (formerly EGF 816), a third generation mutant-selective tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), for the treatment of solid malignancies, with a focus on non-small cell lung cancer. Nazartinib is a covalent mutant-selective EGFR inhibitor, with Ki and Kinact of 31 nM and 0.222 min−1 on EGFR(L858R/790M) mutant, respectively. Upon oral administration, nazartinib covalently binds to and inhibits the activity of mutant forms of EGFR, including the T790M EGFR mutant, thereby preventing EGFR-mediated signaling. This may both induce cell death and inhibit tumor growth in EGFR-overexpressing tumor cells. EGFR, a receptor tyrosine kinase mutated in many tumor cell types, plays a key role in tumor cell proliferation and tumor vascularization. EGF816 preferentially inhibits mutated forms of EGFR including T790M, a secondarily acquired resistance mutation, and may have therapeutic benefits in tumors with T790M-mediated resistance when compared to other EGFR tyrosine kinase inhibitors. As this agent is selective towards mutant forms of EGFR, its toxicity profile may be reduced as compared to non-selective EGFR inhibitors which also inhibit wild-type EGFR.