LAROMUSTINE is a sulfonylhydrazine alkylating agent. It is metabolized to yield a chloroethylating compound (VNP-4090-CE) and a carbamoylating compound (methyl isocyanate). The former is primarily responsible for the antineoplastic effect of LAROMUSTINE. It alkylates the O6 position of guanine, resulting in DNA crosslinking, strand breaks, chromosomal aberrations, and disruption of DNA synthesis. The carbamoylating species contribute to antitumor activity by inhibiting O6-alkylguanine transferase, an enzyme involved with DNA repair. It was studied in the treatment of several types of cancer, however, its development was discontinued.

Tirabrutinib (also known as ONO-4059 or GS-4059), a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor that demonstrated antitumor activity in preclinical models. Tirabrutinib participated in phase I clinical trial in patients with relapsed or refractory B-cell malignancies, where it was well tolerated and showed promising efficacy. In addition, tirabrutinib is involved in phase II clinical trials to study safety and efficacy in adults with Active Sjogren's syndrome and in adults with chronic lymphocytic leukemia. Besides the drug was studied for the treatment of Waldenstrom's macroglobulinemia and patients with refractory pemphigus.

Ionomycin is an ionophore produced by the bacterium Streptomyces conglobatus. The molecules act as a motile Ca2+ carrier and enhances Ca2+ influx by direct stimulation of store-regulated cation entry across biological membranes. It is highly specific for divalent cations. Ion selectivity is as follows: Ca2+ > Mg2+ >> Sr2+ = Ba2+ Binding of Sr2+ and Ba2+ is insignificant and binding to monovalent cations or rubidium is negligible. La2+ is also bound to some extent. Complexation with a cation is always in a 1:1 stoichiometry and pH-dependent. Essentially no binding of Ca2+ occurs below pH 7.0 and maximum binding takes place at pH 9.5. At the micromolar level, ionomycin can activate Ca2+/Calmodulin dependent kinase and phosphatase to stimulate gene expression. Ionomycin has been shown to induce central demyelination, inhibit adrenal bovine TREK-1 channels, and to regulate cell division of mature human B cells [1]. It is used to study the effects of calcium flux on endoplasmic reticulum (ER) stress, mitochodrial stress and intrinsic apoptosis mechanisms. It is also used to stimulate the intracellular production of the cytokines, interferon, perforin, IL-2, and IL-4 usually in conjunction with PMA.

Empesertib (previously known as BAY-1161909) was developed as a selective inhibitor of the serine/threonine monopolar spindle 1 (Mps1) kinase for the treatment of cancer. Empesertib participated in phase I clinical trials in combination with paclitaxel in subjects with advanced malignancies. The studies were terminated because another more successful Mps1 inhibitor was being developed in parallel.

SP-420 is iron chelator developed by University Of Florida Research Foundation for the treatment of iron overload disease

OBP-801 (spiruchostatin A) is an inhibitor of histone deacetylase (HDAC) enzymes, with potential antineoplastic activity. OBP-801 was originally identified as an enhancer of PAI-1 gene expression and was established as a new HDAC inhibitor by a p21 promoter reporter screen. Upon administration, OBP-801 inhibits the activity of HDACs; this results in an accumulation of highly acetylated chromatin histones, the induction of chromatin remodeling and an altered pattern of gene expression. This leads to selective transcription of tumor suppressor genes, tumor suppressor protein-mediated inhibition of tumor cell division and induction of tumor cell apoptosis. This may inhibit proliferation of susceptible tumor cells. HDAC, which is upregulated in many tumor cell types, deacetylates chromatin histone proteins. OBP‑801 induces M‑phase arrest and apoptosis in rhabdomyosarcoma cells. OBP‑801 is expected to show anticancer effect by promoting an expression of tumor suppressor genes in cancer cell and inducing apoptotic and autophagic cell death. The results of pre-clinical studies on OBP-801 indicated the most potent HDAC inhibitory activity as compared to other HDAC inhibitors including and Zolinza® and Istodax®, and its efficacy on a wide range of cancers is expected. Furthermore, Oncolys has been exploring the potential ophthalmic use of OBP-801 in collaboration with Kyoto Prefectural University of Medicine. OBP-801 has been used in trials studying the treatment of solid tumor.

Etripamil is a non-dihydropyridine, L-type calcium channel blocker. Currently, etripamil is in Phase 3 development for the treatment of paroxysmal supraventricular tachycardia. Milestone Pharmaceuticals is also developing etripamil to provide rapid heartbeat control for patients living with atrial fibrillation and acute symptom relief for patients with angina.