LFF-571 is a novel semisynthetic thiopeptide antibiotic with potent activity against a variety of Gram-positive pathogens, including Clostridium difficile. LFF-571 was generally safe and well tolerated in single and multiple oral doses in healthy subjects. There were no deaths, no serious adverse events, and no subject withdrawals due to an adverse event. The most common adverse event was diarrhea, gastrointestinal pain or distension was also noted. Similar to healthy volunteers, patients with C. difficile infections exhibited high fecal concentrations and low serum levels of LFF571. Novartis is developing oral LFF 571 for the treatment of Clostridium difficile infections. LFF 571 binds to bacterial elongation factor Tu (EF-Tu) in domain 2. Phase-II development is ongoing in USA and Canada.

N(ω)-hydroxy-nor-L-arginine (nor-NOHA), an arginase inhibitor, has therapeutic potential in the treatment of cardiovascular and obstructive airway diseases. Nor-NOHA is a reversible, competitive arginase inhibitor. The affinity of nor-NOHA for the to the arginase active site was found in the nanomolar range. Nor-NOHA has proven to be one of the strongest arginase inhibitors. Inhibition by nor-NOHA is ten times more potent on arginase II than on arginase I. The pharmacokinetics of nor-NOHA is characterized by high bioavailability, close to 100% after multiple dose and rapid elimination resulting in t1/2 of 15–30 min after intravenous and intraperitoneal administration to rats. Arginase inhibition with Nor-NOHA increased circulating arginine levels and decreased hepatic damage during liver I/R injury. Arginase blockade represents a potentially novel strategy to combat hepatic I/R injury associated with liver transplantation. Nor-NOHA is under investigation in clinical trial NCT02009527 (Arginase inhibition in ischemia-reperfusion injury).

Derazantinib (ARQ 087) is an investigational, oral, multi-kinase inhibitor designed to preferentially inhibit the FGFR family of kinases with demonstrated activity in FGFR2 genetic alterations, including fusions. In human cancers, FGFRs have been found to be dysregulated by multiple mechanisms, including aberrant expression, mutations, chromosomal rearrangements, and amplifications. FGFR dysregulation has been identified as a driver in a number of cancers, including iCCA, cholangiocarcinoma, bladder, endometrial, breast, gastric, lung and ovarian. Current scientific literature suggests FGFR alterations exist in anywhere from 5% to 40% of these cancers. Derazantinib is a potent FGFR inhibitor that shows strong anti-proliferative activity in cell lines harboring FGFR2 alterations. In clinical testing, the molecule has demonstrated activity in cancerous tumors harboring FGFR2 fusions in iCCA and bladder cancers.

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.