Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

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.

Trans-1-amino-3-[(18)F]fluorocyclobutanecarboxylic acid (also known as Fluciclovine (18F)) was approved under brand name AXUMIN as a radioactive diagnostic agent indicated for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence. Besides, this radioactive compound is used in patients with cervical, ovarian epithelial or endometrial cancers. Fluciclovine F 18 is a synthetic amino acid transported across mammalian cell membranes by amino acid transporters, such as LAT-1 and ASCT2, which are upregulated in prostate cancer cells, but as was shown, this compound has a higher affinity for ASCT2 in comparison with other transporters.

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy against malaria. Artemether is rapidly metabolized into an active metabolite dihydroartemisinin (DHA). The antimalarial activity of artemether and DHA has been attributed to endoperoxide moiety. Artemethe involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Other mechanisms of action for artemether include their ability to reduce fever by production of signals to hypothalamus thermoregulatory center. Now, recent research has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the brain and spinal cord, which is selectively inhibited by artemether, and is distinct from the two already known cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain and spinal cord explains the ability of artemether in relieving pain and reducing fever which is produced by malaria. The most common adverse reactions in adults (>30%) are headache, anorexia, dizziness, asthenia, arthralgia and myalgia.

Uprosertib is an oral potent Akt inhibitor which acts equally on Akt1, Akt2 and Akt3. The drug is under clinical development in combination with trametinib for the treatment of different cancers, including melanoma, myeloma, breast, endometrial, cervical cancer, etc.

Licochalcone A (LicA) is a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch and has a wide spectrum of pharmacological activities such as anti-oxidant, anti-bacterial, anti-viral, and anti-cancer. However, its pharmacological mechanism is not well defined. The anti-Inflammatory effects of LicA on IL-1β-Stimulated human osteoarthritis chondrocytes was reached by activating Nrf2 signaling pathway. LicA showed anti-proliferative and apoptotic effects in breast cancer cells through regulating Sp1 and apoptosis-related proteins in a dose- and a time-dependent manner. In addition, the chemotherapeutic potential of LicA for treatment of human cervical cancer was achieved by inhibition of PI3K/Akt/mTOR signaling.

Mitolactol is a synthetic derivative of hexitol with antineoplastic and radiosensitizing properties. Mitolactol alkylates DNA via actual or derived epoxide groups, resulting in inhibition of DNA and RNA synthesis.

Baicalein is a flavonoid is a component of the traditional herbal remedy known as Chinese skullcap (or Huang Qin), possesses various biological activities. Baicalein is a neuroprotective agent, which is studied in phase I for the treatment of Parkinson’s disease. By modulating of γ-aminobutyric acid (GABA) type A receptors, baicalein promotes nonamyloidogenic processing of amyloid precursor protein (APP), thereby reducing β-amyloid (Aβ) production and improving cognitive performance in models of Alzheimer's disease. By inhibiting the NF-κB signaling pathway, baicalein suppressed cancer cells proliferation and suppressed the viability of human endometrial stromal cells, thus it may provide a novel treatment option for endometriosis. Besides, this compound was evaluated for its ability to inhibit the influenza virus. Experiments on mice have shown that baicalein showed significant effects in preventing death, increasing the mean time to death and reducing the lung virus titer in a dose-dependent manner.

ATSM CU-64 is an agent for imaging hypoxia in tissues. The agent was developed to be used in PET diagnostic imaging of cancer and showed positive results in phase II of clinical trials in patients with cervical cancer.

Misonidazole is a nitroimidazole with radiosensitizing and antineoplastic properties. Exhibiting high electron affinity, misonidazole induces the formation of free radicals and depletes radioprotective thiols, thereby sensitizing hypoxic cells to the cytotoxic effects of ionizing radiation. This single-strand breaks in DNA induced by this agent result in the inhibition of DNA synthesis. The drug also possesses a substantial cytotoxic effect, independent of radiation, which is selectively expressed in hypoxic cells. Misonidazole may be cytotoxic to the normal hypoxic tissues in the human body, making this became a major concern in the clinical application of the drug. Misonidazole leads to strand breaks in cellular DNA and those cells which fail to survive also fail to repair these strand breaks. Misonidazole depletes intracellular glutathione and is more toxic in glutathione depleted cells.