LY2886721 is a BACE inhibitor used for the treatment of Alzheimer's Disease. LY2886721 did not inhibit other aspartyl proteases such as cathepsin D, pepsin, and renin, and reduced Aβ in a dose-dependent manner in HEK293Swe cells and in primary neurons from PDAPP transgenic mice. LY2886721 was the first BACE inhibitor to reach Phase 2 clinical research. Lilly completed six Phase 1 studies of LY2886721’s safety, tolerability, and pharmacology in a total of 150 healthy volunteers and people with Alzheimer’s disease at doses of 1–70 mg. Single and multiple ascending oral dosing was accompanied by repeat CSF sampling in the hours and days thereafter. This was done to assess CSF penetration and target engagement by way of measuring levels of the drug, BACE1 substrate, and BACE1 cleavage products. The compound lowered CSF Aβ40, Aβ42, and sAPPβ concentrations while increasing sAPPα, consistent with expectations for BACE1 inhibition. Fourteen days of daily dosing reduced BACE1 activity by 50–75 percent, and CSF Aβ42 by 72 percent. No safety concerns were apparent in dosing up to six weeks

Inflazyme Pharmaceuticals initially developed HT-0712 as a phosphodiesterase IV (PDE4) inhibitor with anti-inflammatory properties. Now the rights on this drug are wholly owned by Dart NeuroScience. January 2015, Dart NeuroScience completed a phase II trial of HT-0712 for the memory disorders, where were evaluated the efficacy in improving memory and cognitive performance.

Trequinsin is a potent PDE3 inhibitor that inhibits PDE4 and PDE2 at higher concentrations. Trequinsin can block platelet aggregation and also inhibit tissue factor expression in human endothelial cells. Trequinsin can enhance cellular cAMP content, forskolin-induced cAMP synthesis, and renin release in cells.

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).

Ricolinostat is a selective inhibitor of HDAC6 with IC50 value of 4.7 nM. Ricolinostat demonstrated good anti-proliferative activity on different cell lines and clinical models of cancer. The drug is being tested in phase I/II for the treatment of multiple myeloma and lymphoid malignancies and in phase I in patients with breast cancer, gynecological cancer, cholangiocarcinoma, recurrent chronic lymphoid leukemia.

BTZ-043 efficiently inhibits Mtb cell wall synthesis by blocking the decaprenyl- phosphoribose-2′-epimerase (DprE1), necessary for the synthesis of D-Arabinofuranose, a component of arabinogalactan and arabinomannan. Due to this mechanism it is highly selective for Mycobacteria species and does not affect the gut flora. BTZ-043 binds covalently to the enzyme and blocks it irreversibly. BTZ-043 is active against all tested Mtb strains including clinical isolated from MDR and XDR patients. The in vitro MIC ranges between ~0.1 - 80 ng/ml for fast growers, and from 1 - 30 ng/ml for members of the M. tuberculosis complex. In vivo BTZ-043 shows superior activity to INH in mouse models, most prominent after 2 months and thereafter. Synergistic effects with Rifampicin were detected in vitro as well as in vivo. In preclinical toxicology (GLP) studies, BTZ-043 showed a low toxicologic potential, it was well tolerated up to 180 mg/kg in rats. BTZ-043 showed no interaction with the CYP450 enzymes or the hERG channel. Genotoxicity and mutagenicity studies were negative. In vitro metabolism studies implicate an acceptable stability in the human organism with only one main metabolite. Protocols for GMP production in industrial scale are available and high purity of the substance can be achieved easily. Currently the final tolerability studies in two animal models are completed and studies in mice are conducted to better describe the pharmacodynamic drivers.

BMS 777607 is a substituted 2-aminopyridine shown to inhibit the RON and cMet receptor tyrosine kinases, for the treatment of solid tumors. BMS 777607 demonstrated ligand stimulated and constitutive Met phosphorylation, and inhibition of tumor cell proliferation, in preclinical studies. Preclinical data indicated that BMS 777607 inhibited RON, blocking the conversion of micrometastases to overt metastases by boosting antitumor immunity. Bristol-Myers Squibb conducted a phase I/II trial of BMS 777607 for the treatment of advanced solid tumors in Australia. As at December 2016, no recent reports of development had been identified for preclinical development in Cancer in the USA.

Iincyclinide, also known as CMT-3 and COL-3, is an MMP inhibitor and a chemically-modified tetracycline with potential antineoplastic activity patented by Chas. Pfizer & Co. Incyclinide has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture. Incyclinide is an especially effective inhibitor of the growth and viability of filamentous fungi. Unfortunately, in clinical trials, Iincyclinide failed to demonstrate efficacy in Lymphoma, Melanoma, Renal Cell Carcinoma, and some other tumors.

Apabetalone (RVX-208) is a small molecule BET bromodomain inhibitor selective for BRD4-BD2 undergoing clinical development as a potential therapy to enhance ApoA-I production and treat atherosclerosis and prevent cardiovascular disease events. Apabetalone increases apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-Cholesterol) in vitro and in vivo which is believed to provide a new approach to treating atherosclerosis through the stimulation of reverse cholesterol transport. RVX-208 increased the Tm of all BET bromodomains, indicative of binding. RVX-208 competes for acetylated histone H4 peptide binding to both bromodomains of BRD4, similar to JQ-1, but with a preference for BD2 over BD1. RVX-208 also binds to the bromodomains of BRDs 2 and 3 with a similar preference for BD2 (Kd~5–30 nM) over BD1 (Kd~2–3 uM). Treatment of humans for 1 week with oral RVX-208 increased apoA-I, pre-beta-HDL, and HDL functionality. Resverlogix Corp. has commenced a Phase 3 clinical trial in cardiovascular disease patients with type 2 diabetes mellitus with a primary endpoint of time to first occurrence of Major Adverse Cardiac Events (MACE).