Idasanutlin (RG-7388) is a second-generation, orally bioavailable, selective p53-MDM2 antagonist. MDM2 is an important negative regulator of the p 53 tumor suppressor and is expressed at high levels in a large proportion of acute myeloid leukemia (AML). Blocking the MDM2-p53 interaction stabilizes p53 and activates p-53 mediated cell death and inhibition cell growth. Idasanutlin is under clinical trial in phase III for treatment AML and in combinations with others drugs in phase I/II for treatment of multiple myeloma.

GSK2879552 – is an orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival. On October 2016 GlaxoSmithKline plans a phase I/II trial for Myelodysplastic syndromes (Monotherapy, Combination therapy, Second-line therapy or greater) in USA, Canada and Europe (PO) (NCT02929498).

Orilotimod (previously known as Apo 805K1), an antipsoriatic agent that was studied for the treatment of moderate to severe plaque psoriasis. This drug successfully completed phase II clinical trial in the USA. However, information about the further development of this drug is not available.

Tematropium, a muscarinic acetylcholine receptor antagonist that was studied as an antiasthmatic agent. Information about the current use of this compound is not available.

Sitravatinib (MGCD516) is a receptor tyrosine kinases (RTK) inhibitor that blocks a wide array of RTKs known to be amplified/overexpressed in sarcomas, which are key regulators of signaling pathways that lead to cell growth, survival and tumor progression. It is involved in driving sarcoma cell growth with IC50 of 3980 nM and is superior to other multi-kinase inhibitors in inhibiting cell proliferation, RTK phosphorylation, and phosphorylation of downstream effectors. The efficacy of sitravatinib was tested using a wide panel of sarcoma cell lines, including malignant peripheral nerve sheath tumor (MPNST), Ewing sarcoma (A673), osteosarcoma (Saos2), and liposarcoma (DDLS, LS141). Both in vitro and in vivo efficacy sitravatinib was significantly better that the other two multi-kinase inhibitors, imatinib and crizotinib. Sitravatinib treatment not only inhibits tumor cell proliferation at low nanomolar concentrations in vitro but also results significant tumor growth suppression in vivo in mouse xenograft models. Sitravatinib is being evaluated in a Phase 1b dose expansion cohort in selected patients with specific genetic alterations that are drivers of tumor growth, with an initial focus on Non-Small-Cell Lung carcinoma (NSCLC) and in other solid tumors where sitravatinib may confer a benefit. Its efficacy and safety is also being tested in Phase II clinical trials in patients with advanced liposarcoma as a monotherapy and NSCLC in combination with nivolumab.