RI-1 is a cell-permeable RAD51 inhibitor that binds covalently to the protein surface at Cysteine 319. RI-1 disrupts homologous recombination in human cells. Also, it is an inhibitor of Bfl-1 protein. RI-1 represents a powerful tool for future investigations on mechanisms of DNA repair. RI-1 holds promise as an oncologic drug. In a glioma xenograft model, the Rad51 inhibitor RI-1 clearly enhanced the effect of lomustine on tumor growth.

PF-8380 is a potent autotaxin inhibitor with an IC(50) of 2.8 nM in isolated enzyme assay and 101 nM in human whole blood. Inhibition of ATX by PF-8380 led to decreased invasion and enhanced radiosensitization of GBM cells.

R 59 022 (6-[2-[4-[(4-fluorophenyl)phenylmethylene)-1-piperidinyl]ethyl]-7-methyl-5H-thiazolo[3,2-alpha] pyrimidin-5-one) is is an inhibitor of the enzyme 1,2-diacylglycerol (DAG) kinase, which, by inhibiting the conversion of DAG to phosphatidic acid, causes an increase in endogenous DAG levels and the activity of the DAG-dependent enzyme protein kinase C. R 59 022 was found to inhibit diacylglycerol kinase in human red blood cell membranes at concentrations where poly phosphoinositide phosphodiesterase, phosphatidylinositol kinase, and phosphatidylinositol 4-phosphate kinase activity remained unaffected. In intact platelets, R 59 022 inhibits the phosphorylation of OAG to l-oleoyl-2-acetylglyceryl-3-phosphoric acid (OAPA). R 59 022 2 results in a marked elevation of diacylglycerol levels, a decreased formation of phosphatidic acid and an increased protein kinase C activity in thrombin activated platelets. R59022 induced caspase-mediated apoptosis in glioblastoma, melanoma and in cancer cells, but lacked toxicity in noncancerous cells. Intraperitoneal injections of R59022 at 2 mg/kg significantly increases median survival in mouse xenograft models.

N-Methyladenosine (m6A) is a methylated adenine residue and an endogenous urinary nucleoside product of the degradation of transfer ribonucleic acid (tRNA). Adenosine methylation is directed by a large m6A methyltransferase complex containing METTL3 as the SAM-binding sub-unit. In vitro, this methyltransferase complex preferentially methylates RNA oligonucleotides containing GGACU and a similar preference was identified in vivo in mapped m6A sites in Rous sarcoma virus genomic RNA and in bovine prolactin mRNA. More recent studies have characterized other key components of the m6A methyltransferase complex in mammals, including METTL14, Wilms tumor 1 associated protein (WTAP) and KIAA1429. Following a 2010 speculation of m6A in mRNA being dynamic and reversible, the discovery of the first m6A demethylase, fat mass and obesity-associated protein (FTO) in 2011 confirmed this hypothesis and revitalized the interests in the study of m6A. A second m6A demethylase alkB homolog 5 (ALKBH5) was later discovered as well. The biological functions of m6A are mediated through a group of RNA binding proteins that specifically recognize the methylated adenosine on RNA. These binding proteins are named m6A readers. The YT521-B homology (YTH) domain family of proteins (YTHDF1, YTHDF2, YTHDF3, and YTHDC1) have been characterized as direct m6A readers and have a conserved m6A-binding pocket. These m6A readers, together with m6A methyltransferases (writers) and demethylases (erasers), establish a complex mechanism of m6A regulation in which writers and erasers determine the distributions of m6A on RNA, whereas readers mediate m6A-dependent functions. m6A has also been shown to mediate a structural switch termed m6A switch. Considering the versatile functions of m6A in various physiological processes, it is thus not surprising to find links between m6A and numerous human diseases; many originated from mutations or single nucleotide polymorphisms (SNPs) of cognate factors of m6A. The linkages between m6A and numerous cancer types have been indicated in reports that include stomach cancer, prostate cancer, breast cancer, pancreatic cancer, kidney cancer, mesothelioma, sarcoma, and leukemia. The depletion of METTL3 is known to cause apoptosis of cancer cells and reduce the invasiveness of cancer cells, while the activation of ALKBH5 by hypoxia was shown to cause cancer stem cell enrichment. m6A has also been indicated in the regulation of energy homeostasis and obesity, as FTO is a key regulatory gene for energy metabolism and obesity. SNPs of FTO have been shown to associate with body mass index in human populations and occurrence of obesity and diabetes. The influence of FTO on pre-adipocyte differentiation has been suggested. The connection between m6A and neuronal disorders has also been studied. For instance, neurodegenerative diseases may be affected by m6A as the cognate dopamine signaling was shown to be dependent on FTO and correct m6A methylation on key signaling transcripts. The mutations in HNRNPA2B1, a potential reader of m6A, have been known to cause neurodegeneration.

10-deactyltaxol (10-deacetylpaclitaxel) is a naturally occurring taxane related to taxol (paclitaxel). Taxol is an antitumor drug with cytotoxic properties that correlate with its microtubule-stabilizing activities. When compared to paclitaxel 10-deacetyltaxol is 100% as active as paclitaxel in promoting in vitro microtubule assembly, but is only 30% as cytotoxic as paclitaxel. 10-deactyltaxol is a semi-synthetic precursor of paclitaxel and considered to be paclitaxel impurity. 10-deactyltaxol, isolated from the bark of Taxus brevifolia, was converted into paclitaxel in one composite step (trimethylsilylation, acetylation, and desilylation) and in an overall yield of 80-85%.

Esculin (Esculoside), a coumarin compound derived from the horse chestnut and the traditional Chinese herbs such as Cortex Fraxini, has long been used for treating inflammatory and vascular diseases. The main activities of Esculoside focus on capillary protection, as it improves capillary permeability and fragility. It is reported to inhibit catabolic enzymes such as hyaluronidase and collagenase, thus preserving the integrity of the perivascular connective tissue. Esculin has various biological activities including anti-oxidant activity, intestinal anti-inflammatory activity, anti-cancer activity and growth inhibition of human leukemia cells. Esculin inhibits lipid peroxidation and scavenges hydroxyl radicals in the rat liver and exerts anti-inflammatory activity in both carrageenan- and zymosan-induced paw edema in mice. Esculin has the gastroprotective effect in cold-restraint stress and pylorus ligation-induced ulcer models. Esculin is used in a microbiology laboratory to aid in the identification of bacterial species (especially Enterococci and Listeria).

Dianhydrogalactitol (VAL-083 or NSC-132313) a cytostatic sugar derivative, is alpha,omega-substituted hexitol acting as bifunctional alkylating agent. It induces interstrand crosslinks at N7 guanines leading to doublestrand breaks and HR activation independent of MGMT, and mediating cell cycle arrest through p53-dependent and p53-independent pathways. Dianhydrogalactitol is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer. The drug has not been approved for any indication outside of China. DelMar Pharmaceuticals is developing dianhydrogalactitol for the treatment of intracranial tumors.

Fluspirilene, a neuroleptic drug, which is used clinically to treat schizophrenic patients, by blocking of dopamine receptors, especially the dopamine D2 receptors. Fluspirilene also displays calcium channel-blocking activity; it inhibits glutamate release primarily by reducing presynaptic Ca2+ influx via N-type Ca2+ channels that also may contribute to the antischizophrenic action of the drug. Recently in the frame of a project of drugs repositioning, fluspirilene was studied as an anti-cancer drug. It was found, that fluspirilene demonstrates a significant inhibitory effect on the proliferation and invasion of glioma cells. Thus, it can be a promising drug for the treatment of glioblastoma. In addition, fluspirilene, as a potential cyclin-dependent kinase 2 inhibitor, was investigated in animal models for the treatment of human hepatocellular carcinoma. Taken into account that fluspirilene has a long history of safe human use, the drug can be applicable in clinical therapy for cancer’s disease immediately.

Semustine is a methylated derivative of carmustine with potent antineoplastic activity. As an alkylating agent, semustine forms covalent linkages with nucleophilic centers in DNA, causing depurination, base-pair miscoding, strand scission, and DNA-DNA cross-linking, which may result in cytotoxicity. Semustine is primarily used to treat brain tumors, colorectal tumors, lymphomas, and stomach cancer.

Tivozanib (formerly AV-951, KRN-951) is a potent and selective VEGFR tyrosine kinase inhibitor and inhibits angiogenesis and vascular permeability in tumor tissues. It completed phase III a trial investigation for the treatment of renal cell carcinomas, but has not been still approved. In addition, this drug is in the phase II of clinical trial for the investigation it in patients with glioblastoma and colorectal carcinoma.