Diosmetin is the aglycone of the flavonoid glycoside diosmin, which occurs naturally in citrus fruits. Diosmetin is found in the legume Acacia farnesiana Wild and Olea europaea L. leaves. Diosmin is hydrolyzed to its aglycone diosmetin by intestinal microflora enzymes before its absorption into the body. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic and anti-inflammatory activities. Diosmetin increased inhibitory GSK-3beta phosphorylation, while selectively reducing gamma-secretase activity, Abetta generation, tau hyperphosphorylation and pro-inflammatory activation of microglia in vitro, without altering Notch processing. Therefore, diosmetin could be considered as potential candidate for novel anti- Alzheimer's disease therapy. Diosmetin is ER-beta agonist and potential novel drug for the acute myeloid leukemia treatment.

Roquinimex (Linomide, LS 2616) is a quinoline-3-carboxamide with pleiotropic immune modulating capacity and it has therapeutic effects in several experimental animal models of autoimmune diseases. Linomide has been evaluated in clinical trials for multiple sclerosis, and was indeed shown to have disease inhibitory effects. However, due to unexpected side effects recorded in patients treated with Linomide, premature termination of clinical trials was required. The basic mechanism(s) of action of Linomide in inducing beneficial effects in autoimmune diseases is still elusive. Some experimental evidence indicates that Linomide influences the regulation of the cytokine profile, resulting in the inhibition of autoimmune and inflammation pathologies. Roquinimex possesses potential antineoplastic activity. Roquinimex inhibits endothelial cell proliferation, migration, and basement membrane invasion; reduces the secretion of the angiogenic factor tumor necrosis factor alpha by tumor-associated macrophages (TAMs); and inhibits angiogenesis. Roquinimex was in phase III clinical trials with Pharmacia Corporation in Europe and the US for the treatment of multiple sclerosis.

Enocitabine is an anti-cancer nucleoside that was developed for the treatment of acute myeloid leukemia. Although the exact mechanism of its action is unknow, Enocitabine effectively inhibits tumor cell growht in vitro and the inhibition is supposed to be related to its metabolism to Ara-C, an inhibitor of DNA polymerase. The drug was approved in Japan and Korea and was marketed under the name Sunrabin, however, its current marketing status is unknown and is assumed to be discontinued.

Vosaroxin is a small molecule and a naphthyridine analogue with antineoplastic activity. This quinolone-based topoisomerase II inhibitor is a new therapeutic for acute myeloid leukemia (AML). Being a DNA intercalating topoisomerase II inhibitor that causes the induction of apoptosis via double-strand DNA breaks vosoroxin is chemically distinct from other topoisomerase inhibitors with its stable quinolone-based core. Due to the stability of this core, vosaroxin is not associated with significant formation of toxic metabolites, free radicals, or reactive oxygen species, which are associated with off-target organ damage and cardiotoxicity. Furthermore, vosaroxin evades two common mechanisms of drug resistance, as it is not a substrate for the P-glycoprotein efflux pump and its activity is maintained in cells with p53 deletion. Vosaroxin has beeт tested in several investigator-sponsored studies, both as a single-agent and in combination with other therapies, for the treatment of AML and myelodysplastic syndromes. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction. The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

Treosulfan (l-threitol-1,4-bis-methanesulfonate; dihydroxybusulfan) is a prodrug of a bifunctional alkylating cytotoxic agent that is approved for the treatment of ovarian carcinomas in a number of European countries. The antitumor activity of treosulfan has been shown in a variety of solid tumors. It is used for the treatment of all types of ovarian cancer, either supplementary to surgery or palliatively. Treosulfan is a prodrug that is converted nonenzymatically first to a mono-epoxide – (2S,3S)- 1,2-epoxy-3,4-butanediol-4-methanesulfonate – and then to a diepoxide – l-diepoxybutane, which is also a metabolite of butadiene – under physiological conditions. Such conversions are assumed to account for the alkylating and therapeutic activities of treosulfan.

Quizartinib (AC220) is an orally bioavailable, small molecule receptor tyrosine kinase inhibitor that is being developed by Daiichi Sankyo Company (previously Ambit Biosciences) and Astellas Pharma as a treatment for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and advanced solid tumours. The highest affinity target identified for Quizartinib was FLT3. The only other kinases with binding constants within 10-fold that for FLT3 were the closely related receptor tyrosine kinases KIT, PDGFRA, PDGFRB, RET, and CSF1R. Kinase inhibition of (mutant) KIT, PDGFR and FLT3 isoforms by quizartinib leads to potent inhibition of cellular proliferation and induction of apoptosis in in vitro leukemia models as well as in native leukemia blasts treated ex vivo.

Quizartinib (AC220) is an orally bioavailable, small molecule receptor tyrosine kinase inhibitor that is being developed by Daiichi Sankyo Company (previously Ambit Biosciences) and Astellas Pharma as a treatment for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) and advanced solid tumours. The highest affinity target identified for Quizartinib was FLT3. The only other kinases with binding constants within 10-fold that for FLT3 were the closely related receptor tyrosine kinases KIT, PDGFRA, PDGFRB, RET, and CSF1R. Kinase inhibition of (mutant) KIT, PDGFR and FLT3 isoforms by quizartinib leads to potent inhibition of cellular proliferation and induction of apoptosis in in vitro leukemia models as well as in native leukemia blasts treated ex vivo.

Selinexor (KPT-330) is a first in class XPO1 antagonist being evaluated in multiple later stage clinical trials in patients with relapsed and/or refractory hematological and solid tumor malignancies.

PF-04449913 is a potent and selective inhibitor of the Hh signaling pathway through binding to the target, smoothened. PF-04449913 inhibits Hh signaling in vitro and has demonstrated significant antitumor activity in vivo. In the clinic, PF-04449913 is being evaluated both in hematological and solid malignancies, with a phase II trial currently underway in both fit and unfit patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Treatment-related adverse-events were nausea, dizziness, somnolence, QT prolongation and pruritus. Based on pre-clinical assessments, CYP3A4 is believed to be primarily involved in the metabolism of PF-04449913 that is why PF-04449913 plasma exposures and peak concentrations were increased following concurrent administration of ketoconazole (CYP3A4 inhibitor).

PF-04449913 is a potent and selective inhibitor of the Hh signaling pathway through binding to the target, smoothened. PF-04449913 inhibits Hh signaling in vitro and has demonstrated significant antitumor activity in vivo. In the clinic, PF-04449913 is being evaluated both in hematological and solid malignancies, with a phase II trial currently underway in both fit and unfit patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Treatment-related adverse-events were nausea, dizziness, somnolence, QT prolongation and pruritus. Based on pre-clinical assessments, CYP3A4 is believed to be primarily involved in the metabolism of PF-04449913 that is why PF-04449913 plasma exposures and peak concentrations were increased following concurrent administration of ketoconazole (CYP3A4 inhibitor).