Oprozomib (PR-047) is an orally bioavailable derivative of carfilzomib, with similar biological activity, i.e. inhibition of the chymotrypsin-like activity of the proteasome. It inhibits the activity of the proteasome, thereby blocking the targeted proteolysis normally performed by the proteasome; this may result in an accumulation of unwanted or misfolded proteins. Disruption of various cell signaling pathways may follow, eventually leading to the induction of apoptosis and inhibition of tumor growth. Oprozomib (PR-047) is being investigated for the treatment of hematologic malignancies, specifically, multiple myeloma, with Phase I/II trial ongoing.

Ilorasertib (previously known as ABT-348), an orally bioavailable ATP-competitive inhibitor of Aurora kinases (A, B and C), as well as the VEGF and PDGF families of receptor tyrosine kinases, was developed by AbbVie as an antineoplastic agent. It is known that Aurora kinases A, B, and C play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types. Both VEGFRs and PDGFRs may be upregulated in various tumor cell types. Ilorasertib alone or in combination with azacitidine demonstrated activity in preclinical models in various hematological malignancies, indicating that pan-Aurora kinase and multiple kinase inhibition may have preferential antileukemic activity. Ilorasertib participated in phase I clinical for patients with advanced hematologic malignancies. The result has shown that the drug could be further studied in acute myelogenous leukemia. Ilorasertib is also going to be studied in phase II clinical trials to learn if this drug can help to control CDKN2A-deficient cancer in patients with advanced cancers.

Emixustat (formerly ACU-4429) is a nonretinoid compound with a unique mode of action in the retinal pigment epithelium, where it modulates the biosynthesis of visual chromophore through its effect on retinal pigment epithelium protein 65 (RPE65). Emixustat modulates the visual cycle by inhibiting a critical enzyme of this pathway RPE65. Acucela Inc., a Kubota Pharmaceutical company, is developing emixustat for the treatment of Stargardt disease and proliferative diabetic retinopathy.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

WP1066 is a cell-permeable AG490 tyrphostin analog that effectively inhibits the phosphorylation of Janus kinase 2 (JAK2) and its downstream signal transducer and activator of transcription 3 (STAT3) in a dose- and time-dependent manner. As a result, WP1066 concentrations in the low micromolar range induced time- and dose-dependent antiproliferative and proapoptotic effects in cancer cells. WP1066 has been used in Phase I trial studying the treatment of melanoma, brain cancer, solid tumors, and central nervous system neoplasms.

Napabucasin (BBI608) is an orally administered small molecule that blocks stem cell activity in cancer cells by targeting the signal transducer and activator of transcription 3 pathway, which is over-activated in many types of cancer and has been shown to be an important pathway in cancer stem cell-mediated propagation of cancer. Napabucasin has already shown promising efficacy on different cancer types, both as a monotherapy and in combination with conventional chemotherapeutic agents. Early-phase trials have shown promising anti-tumor efficacy when patients are treated with napabucasin in combination with standard chemotherapy agents, and preclinical results suggest that napabucasin can synergize with chemotherapy agents, such as paclitaxel, to potentially overcome drug resistance. Encouraging phase Ib/II trial results warrant further clinical study with napabucasin and paclitaxel combination therapy, especially in malignancies where there is an urgent and unmet need for effective therapeutics, such as in patients with advanced pancreatic adenocarcinoma.

LCQ908 (Pradigastat) is a diacylglycerol acyltransferase-1 (DGAT-1) inhibitor. DGAT-1 is one of the two DGAT enzymes that catalyse the formation of triglycerides from diacylglycerol and acyl- coenzyme A. DGAT-1 catalyses the final committed step in processing dietary fatty acids into triglycerides carried on chylomicrons for transport around the body. Pradigastat may decrease the level of triglycerides in the blood and is intended for the first line treatment of FCS. It is administered orally at 10-40mg daily in addition to a low fat diet. Pradigastat is also in phase II clinical trials for type 2 diabetes and severe hypertriglyceridaemia (familial hyperchylomicronaemia phenotypes I and V). Pradigastat is a designated orphan drug in the EU. In a phase III clinical trial.

NM404 I-131 (also known as CLR 131) is a phospholipid ether analog labeled with iodine I-131, used as radiotherapeutic and positron emission tomography (PET) radioimaging agent. Upon infusion, the drug accumulates in tumor cells and is retained for a long time because of the decreased activity of a phospholipase D. The drug is being developed by Cellectar Biosciences and is investigated in clinical trials against multiple myeloma and hematologic malignancies. In 2014, the FDA granted orphan drug designation for CLR 131 for the treatment of multiple myeloma.