APC-3316 is a vinyl sulfone cystein protease inhibitor. It is a potent, irreversible cysteine protease inhibitor and a potent and selective CCR4 antagonist. Its therapeutic targets are cruzain, a cysteine protease of the protozoan parasite Trypanosoma cruzi, and cathepsins B and L, which are associated with cancer progression. It was discontinued after preclinical trials in Chagas disease in USA.

GGTI-2418, also known as PTX100, is a synthetic peptidomimetic inhibitor of geranylgeranyltransferase I (GGTase I) that appears to induce apoptosis by downregulating several pivotal oncogenic and tumor survival pathways. In preclinical studies, GGTI-2418 has been shown to cause significant breast tumor regression in ErbB2 transgenic mice model. GGTI-2418 was the first GGTase I inhibitor to enter clinical development in early 2009. Phase I clinical trials early results demonstrated that ~30% of patients with advanced solid tumors had stable disease following GGTI-2418 therapy, the compound was well-tolerated and had minimal toxicity. However, the Phase I trial of GGTI-2418 has been stopped due to its lack of efficacy in patients. In February 2015 Prescient Therapeutics in-licensed the p27 biomarker for use as a companion diagnostic. Patients with low levels of p27 are more likely to respond to GGTI-2418 therapy.

SNX-2112, a novel 2-aminobenzamide inhibitor of heat shock protein 90 (Hsp90) was discovered by Serenex. This drug was investigated for treatment of different cancer cell lines, including hepatocellular carcinoma cells, breast cancer cells and in combination with 5-fluorouracil in esophageal cancer. However, subsequent development has been discontinued due to ocular toxicity as identified in a phase I study.

RG2833 is a compound originally developed by the Scripps Insitute for the treatment of Friedrick's Ataxia. RG2833 is a potent and selective inhibitor of neuronal histone deacetylase. RG2833 has been granted orphan drug status has been investigated in phase one clinical trials. There has also been proof of concept studies conducted for the treatment of Parkinson's disease.

JNJ-28312141 is an orally active colony-stimulating factor-1 receptor and FMS-related receptor tyrosine kinase-3 inhibitor. In preclinical models, JNJ-28312141 caused regression of ITD-FLT3–dependent MV-4-11 AML xenografts. The drug also suppressed the growth of H460 non-small cell lung adenocarcinoma xenografts and inhibited osteoclastogenesis and osteolysis in a rat model of metastatic bone disease.

RG3039, also known as PF-06687859, is the first small molecule developed specifically for treatment of Spinal muscular atrophy (SMA). This drug is used in SMA patients that have reached early stage clinical trials. It was shown that RG3039 improved survival, function and motor unit pathologies in SMA mouse models. It is known, that RG3039 is a potent inhibitor of the mRNA decapping scavenger enzyme (DcpS). DcpS is a nuclear shuttling protein that binds and hydrolyzes the m(7)GpppN mRNA cap structure and a modulator of RNA metabolism. Therefore, DcpS represents an intrigueing therapeutic target for modulating gene expression by a small molecule. The exact therapeutic mechanism remains unknown.

Bromopyruvate is an halogenated analogue of pyruvic acid known as an alkylating agent reacting with thiol groups of many proteins. Bromopyruvate exerts anticancer action. It is based on the impairment of energy metabolism of tumor cells by inhibiting enzymes in the glycolysis pathway (hexokinase II, glyceraldehyde 3-phosphate dehydrogenase, phosphoglycerate kinase) and the oxidative phosphorylation (succinate dehydrogenase). Bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Treatment with bromopyruvate has been administered in several cancer type models both in vitro and in vivo, either alone or in combination with other anticancer therapeutic approaches. These studies clearly demonstrate bromopyruvate broad action against multiple cancer types. This compound has also antifungal and antiparasitic activity.

Myriocin ((2S,3R,4R,6E)-2-amino-3,4- dihydroxy-2-(hydroxymethyl)-14-oxo-6-eicosenoic acid, ISP-1, thermozymocidin) is a small-molecule immunosuppressant, isolated from the Mycelia sterilia thermophilic fungus. Myriocin inhibits serine palmitoyltransferase (SPT) at picomolar concentrations blocking synthesis of ceramide, a precursor of sphingomyelin (SM) and glycosphingolipids. Inhibition of hepatic serine palmitoyl transferase reduces plasma sphingomyelin levels in the absence of changes in cholesterol or triglyceride (TG) concentration and this leads to a reduction of atherosclerosis. In preclinical studies, Myriocin treated mice shows significant reductions in both plasma SM and Glycosphingolipids (GSL) concentration. Moreover, SM and GSL concentrations were significantly correlated, indicating that SPT inhibition suppresses the synthesis of both these sphingolipids concomitantly. The inhibition of atherosclerosis induced by myriocin was not associated with changes in plasma cholesterol or TG concentrations or lipoprotein profiles.

Boldine, an aporphine alkaloid, found abundantly in the leaves/bark of boldo (Peumus boldus Molina) widely consumed in the folk medicine of some regions. Boldine possesses various pharmacological properties including, anticancer activity. It exhibits a significant improvement of learning and memory through inhibition of brain acetylcholinesterase activity and alleviation of brain oxidative stress, which was shown on animal models. Boldine is a potentially useful agent for the treatment of leishmaniosis. In addition, it suppresses osteoclastogenesis, improves bone destruction and may be a potential therapeutic agent for rheumatoid arthritis. Besides, was shown, that boldine inhibits telomerase in cells treated with sub-cytotoxic concentrations. Telomerase inhibition occurs via down-regulation of human telomerase reverse transcriptase (hTERT), the catalytic subunit of the enzyme.