KU0058948 is an inhibitor of Poly(ADP-ribose) polymerase (PARP). In addition KU0058948 was shown to activate extracellular signal-regulated kinase 8 (ERK8). It affects viability of leukemia, pancreatic and endometrial cancer cells.

JANEX-1 (WHI-P131), a selective Janus kinase 3 (JAK3) inhibitor, has been shown to delay the onset of diabetes in the NOD mouse model. It is a cell-permeable, reversible, potent, ATP-competitive, and specific inhibitor of JAK3 (IC50 = 78 uM); has no effect on JAK1, JAK2, or Zap/Syk or SRC tyrosine kinases. JANEX-1 has a potent inhibitory effect on cytokine-induced β-cell damage. JANEX-1 has a therapeutic potential in the treatment and prevention of type 1 diabetes. JANEX-1 induced apoptosis in JAK3-expressing human leukemia cell lines NALM-6 and LC1. JANEX-1 inhibited the clonogenic growth of JAK3-positive leukemia cell lines DAUDI, RAMOS, LC1;19, NALM-6, MOLT-3, and HL-60 (but not JAK3-negative BT-20 breast cancer, M24-MET melanoma, or SQ20B squamous carcinoma cell lines) in a concentration-dependent fashion. Potent and specific inhibitors of JAK3 such as JANEX-1 may provide the basis for the design of new treatment strategies against acute lymphoblastic leukemia, the most common form of childhood cancer. JANEX-1/WHI-P131 also showed potent anti-inflammatory activity in several cellular and in vivo animal models of inflammation, including mouse models of peritonitis, colitis, cellulitis, sunburn, and airway inflammation with favorable toxicity and pharmacokinetic profile. JANEX-1 may prove useful to prevent or alleviate the symptoms of endometriosis (EMS).

Calactin and calotropin were the major cardenolides in Danaus plexippus reared on A. fruticosa or A. curassavica. It was discovered, that calactin could be potential anticancer compound that was supported for human leukemia cells. It was shown, that calactin decreased the expression of cell cycle regulatory proteins Cyclin B1, Cdk1, and Cdc25C was consistent with a G2/M phase arrest. Furthermore, calactin induced extracellular signal-regulated kinase (ERK) phosphorylation, activation of caspase-3, caspase-8, and caspase-9, and PARP cleavage.

BAY 61-3606 is a potent inhibitor of spleen tyrosine kinase (Syk) which is playing essential roles in receptors for Fc portion of immunoglobulins and B cell receptor complex signaling in various inflammatory cells. In addition, BAY61-3606 could inhibit the inhibitor of nuclear factor kappa B kinase (IKK-alpha) kinase activity. The compound is able to inhibit neoplastic phenotype of leukemia cells as well as of colon and breast cancer cells in vitro. BAY 61-3606 also exrets antiinflammatory and antiallergic properties in animal models.

Canthin-6-one is a natural product isolated from various plant genera and from fungi with potential antitumor activity. It induces cell death, cell cycle arrest and differentiation in human myeloid leukemia cells. Canthin-6-one is main compound isolated from Zanthoxylum chiloperone var angustifolium with broad spectrum antifungal, leishmanicidal and trypanocidal activities. Canthin-6-one exhibited trypanocidal activity in vivo in the mouse model of acute or chronic infection. Canthin-6-one exhibited a broad spectrum of activities against Aspergillus fumigatus, A. niger, A. terreus, Candida albicans, C. tropicalis, C. glabrata, Cryptococcus neoformans, Geotrichum candidum, Saccharomyces cerevisiae, Trichosporon beigelii, Trichosporon cutaneum and Trichophyton mentagrophytes var. interdigitale with MICs values between 5.3 and 46 umol/L.

Neopterin is a byproduct of the tetrahydrobiopterin (BH4) biosynthetic pathway, which requires Mg2+, Zn2+, and NADPH as cofactors. Tetrahydrobiopterin is an obligatory cofactor for phenylalanine, tyrosine, tryptophan hydroxylases and alkylglycerol monooxygenase, and for all isoforms of nitric oxide synthase (NOS). BH4 is synthesized by multiple metabolic routes, namely the de novo, salvage and recycling pathways. The de novo via generates BH4 from guanosine triphosphate (GTP) by the concert action of guanosine triphosphate Cyclohydrolase I (GTPCH), 6-pyruvoyl Tetrahydropterin synthase (PTPS) and sepiapterin reductase. GTPCH catalyzes the conversion of GTP to 7,8-dihydroneopterin triphosphate. Then, Alkaline Phosphatases removes the phosphates to generate, 8-dihydroneopterin, which is further converted to Neopterin by non-enzymatic oxidation. Neopterin is a recognized biomarker for immune system activation. IFN-g, which is released from activated Th1 cells during the initiation of the immunological cellular response, is one of the main stimuli for neopterin formation. The source of neopterin in the central nervous system (CNS) is not well understood. The evidence available in the literature has suggested that neopterin crosses the blood-brain barrier, therefore the CSF levels may reflect the serum or plasma neopterin concentrations. Cell culture studies strongly suggest that neopterin is not an inert compound, but a cytoprotective molecule synthesized and secreted by nerve cells as a response to damage or inflammation.

Wikstromol is the enantiomer of nortrachelogenin, isolated from Trachelospermum asiaticum var. intermedium and Pinus palustris. Wikstromol exhibited acetylcholinesterase (AChE) inhibitory. It has been found to be active against P-388 lymphocytic leukemia growth implanted in mice. The reason for this is at present unclear, although it is possible that wikstromol is either metabolized to an active antileukemic agent by the host or else serves as a biological response modifier.

IMB-10 stabilizes binding of alpha(M)beta(2) to its endogenous ligands proMMP-9 and fibrinogen. It inhibited alpha(M)beta(2)-dependent migration in vitro and inflammation-induced neutrophil emigration in vivo. IMB-10 therapy inhibited the growth of both leukemia and lymphoma xenografts and significantly prolonged the survival of the mice with lymphoma. IMB-10 has potential as a therapy for leukocytic malignancies, particularly for lymphomas.

GW-311616, a specific NE inhibitor, may act as a potential targeted drug for leukemia, which may have a profound impact on the future of leukemia-targeted therapy. GW-311616 hydrochloride is a potent, selective, intracellular, orally bioavailable and long duration inhibitor of human neutrophil elastase (HNE) with an IC50 value of 22nM. GW-311616 hydrochloride has been found to be selevtive over other human serine proteases with IC50 values of 22nM for HNE, >100uM for trypsin, cathepsin G, and plasmin, >3uM for chymotrypsin and tissue plasminogen activator. In HNE enzyme kinetic tests, GW-311616 has been reported to inhibit HNE with a Ki value of 0.13nM. In addition, GW-311616 has been revealed to inhibit HWB with an IC50 values of 0.67uM in HWB assay. Moreover, by measurement of intraneutrophil elastase activity, GW-311616 hydrochloride has been suggested to have a dose-response and duration of action in blood samples of dog. At present, although research on GW-311616 has being dropped at the preclinical stage, the beneficial profile of oral GW-311616 may make it usuful in the design of new drugs.

Pinometostat, trans- (9H-Purin-6-amine, 9-[5-deoxy-5-[[trans-3-[2-[6-(1,1-dimethylethyl)-1H-benzimidazol-2-yl]ethyl]cyclobutyl](1-methyl ethyl)amino]-β-D-ribofuranosyl]-) is an isomer of Pinometostat, a small molecule inhibitor of histone methyltransferase with potential antineoplastic activity. Pinometostat, trans-specifically blocks the activity of the histone lysine-methyltransferase DOT1L, thereby inhibiting the methylation of nucleosomal histone H3 on lysine 79 (H3K79) that is bound to the mixed lineage leukemia (MLL) fusion protein which targets genes and blocks the expression of leukemogenic genes.