PIK-75 is a specific inhibitor of the p110 α isoform of phosphatidylinositol-3-kinase, an enzyme which is upregulated in several human cancers. PIK-75 is a p110α inhibitor with IC50 of 5.8 nM (200-fold more potently than p110β), it is also an inhibitor of CDK9. Cell-based assays revealed that PIK-75 potently and dose dependently inhibits in vitro and in vivo production of TNF-alpha and IL-6, diminishes the induced expression of human endothelial cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and blocks human monocyte-endothelial cell adhesion. Most importantly, PIK-75, when administered orally in a therapeutic regimen, significantly suppresses the macroscopic and histological abnormalities associated with dextran sulfate sodium-induced murine colitis. The efficacy of PIK-75 in attenuating experimental inflammation is mediated, at least in part, due to the downregulation of pertinent inflammatory mediators in the colon. Collectively, these results provide first evidence that PIK-75 possesses anti-inflammatory potential. Given that PIK-75 is known to exhibit anti-cancer activity, the findings from this study thus reinforce the cross-therapeutic functionality of potential drugs.

PP-242 is a selective mTOR inhibitor with IC50 of 8 nM. mTOR has emerged as an important drug target, and PP-242 is the first selective and ATP competitive inhibitor of mTOR that has been described. Unlike rapamycin, PP-242 inhibits both mTORC1 and mTORC2. PP-242 suppresses bladder cancer cell proliferation and migration through deactivating the mammalian target of rapamycin complex 2/AKT1 signaling pathway. PP242 also inhibits several protein kinases including PKC, RET and JAK2 kinases. PP-242 shows strong antitumor activity in a pheochromocytoma PC12 cell tumor model. PP-242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway. PP-242 induces apoptosis in AML cells under conditions mimicking the bone marrow microenvironment.

AST-487 is an inhibitor of RET (IC50 = 0.88 uM), FLT3 (Ki = 0.52 uM), KDR (IC50 = 0.17 uM), c-Abl (IC50 = 0.02 uM), and c-Kit (IC50 = 0.5 uM). AST-487 has potent and selective antiproliferative effects 7 on primary AML patient cells and cell lines expressing FLT3-ITD or FLT3 kinase domain point mutants. AST-487, which selectively targets mutant FLT3 protein kinase activity, is also shown to override PKC412 resistance in vitro, and has significant antileukemic activity in an in vivo model of FLT3-ITD(+) leukemia. Finally, the combination of NVP-AST487 with standard chemotherapeutic agents leads to enhanced inhibition of proliferation of mutant FLT3-expressing cells. AST-487 displays high selectivity and potency toward FLT3 as a molecular target, and could potentially be used to override drug resistance in AML.

One of the most important trichothecene, verrucarin J produced by several genera of fungi that may contaminate foods of both human and animal. Verrucarin J has shown cytotoxic activity in human HL-60 cell line and murine L1210 cell line.

Oridonin is a diterpenoid purified from Rabdosia rubescens. In traditional Chinese medicine oridonin powder (Donglingcao herb extract) is used as an over-the-counter medicine because of its anti-tumor, anti-bacterial, anti-inflammatory, analgesic and other effects. Oridonin was shown to inhibit many tumor cell lines in vitro and its mechanism of action is mainly explained by inhibition of NF-kB signaling, Keap1-Nrf2-ARE pathway and upregulation of p53/p21 signaling and ROS production.

MK-8776 (SCH-900776) is a checkpoint kinase 1 inhibitor which was developed by Merck for the treatment of cancer. The drug was tested in phase II clinical trials on patients suffering from acute myeloid leukemia (in combination with cytarabine) and in phase I on patients suffering from solid tumors or lymphoma (as monotherapy and in combination with gemcitabine).

Alantolactone and isoalantolactone, main bioactive compounds that are present in many medicinal plants such as Inula helenium, L. Inula japonica, Aucklandia lappa, Inula racemosa, and Radix inulae, have been found to have various pharmacological actions including anti-inflammatory, antimicrobial, and anticancer properties, with no significant toxicity. Alantolactone and isoalantolactone have been reported for their wide spectrum of biological effects, including antifungal, anthelmintic activities, antimicrobial activities, anti-inflammatory activities, antitrypanosomal activities, and antiproliferative effects on several cancer cell lines, such as colon, melanoma, ovary, prostate, lung, and leukemia. Alantolactone isolated from Inula helenium (Compositae), a traditional Chinese medicinal herb, provides an effective inhibitory activity for cell growth against MK-1, HeLa, B16F10, and K562 cell lines. Many other human cancer cell lines, including U87 glioma cells, Bel-742, SMMC-7721 and HepG2 liver cancer cells, PANC-1 pancreatic carcinoma cells, A59 lung cancer cells, colon adenocarcinoma HCT-8 cells, CNS cancer cell line SF-295, leukemia HL-60, Hepa1c1c7 cells, BPRc1 Hepatic cancer cells, and HCT-8 colon cancer cells, have also been reported for apoptosis caused by alantolactone.

Toyocamycin is a nucleoside- type antibiotic analogue of adenosine, isolated from Streptomyces species. Toyocamycin is an antibiotic first isolated by Nishimura et al. from a new species of Streptomyces (St. toyocaensis), with a rather specific antibiotic spectrum. It strongly inhibits Candida albicans and Mycobacterium tuberculosis, without notable action on other microorganisms, such as many gram-positive and gramnegative bacteria, fungi, and yeast. Toyocamycin is an anti-tumor antibiotic with various target activities. Toyocamycin is a potent inhibitor of RNA self-cleavage in mammalian cells. It also inhibits phosphatidylinositol kinase, a cell proliferation regulator. Toyocamycin can suppress thapsigargin-, tunicamycin- and 2-deoxyglucose-induced XBP1 mRNA splicing in HeLa cells. This suppression doesn’t affect the activating of transcription factor 6 (ATF6) and PKR-like ER kinase (PERK)’s activation. Toyocamycin prevents IRE1a-induced XBP1 mRNA cleavage in vitro. In mammalian cells, toyocamycin inhibits RNA synthesis. Toyocamycin induces apoptosis of MM cells including bortezomib-resistant cells at nanomolar levels in a dose-dependent manner. It also inhibited growth of xenografts in an in vivo model of human multiple myeloma. It is also a lead compound for developing anti-MM therapy and XBP1 as an appropriate molecular target for anti-multiple myeloma therapy. Toyocamycin was the first identified small-molecule inhibitor of Rio1, showing mixed inhibition. This mode of action of toyocamycin results from its dual activity towards the Rio1 kinase. On the one hand, toyocamycin acts as an ATP-competitive inhibitor, and on the other hand, it stabilizes the less catalytically active oligomeric isoform of the Rio1 kinase.

Parthenolide is a sesquiterpene lactone found in Tanacetum that exhibits anticancer chemotherapeutic, anti-metastatic, anti-angiogenic, anti-inflammatory, and antinociceptive activities. Parthenolide acts as a partial agonist at transient receptor potential ankyrin 1 (TRPA1) channels and desensitizes them, preventing release of calcitonin gene-related peptide (CGRP). Additionally, parthenolide inhibits ATPase activity of NLRP3 and protease activity of caspase 1. In multiple myeloma cells, parthenolide decreases expression of NF-κB, VEGF, and IL-6 and increases expression of IκB kinase, inhibiting cell migration and tubule formation. In non-small cell lung cancer (NSCLC) cells, parthenolide decreases levels of MCL-1 and increases levels of MAIP-1, triggering ER stress and inducing cell cycle arrest and apoptosis. In breast cancer cells, this compound activates NADPH oxidase and increases ROS generation, increasing levels of p-JNK and downregulating NF-κB, VEGF, and matrix metalloproteinases 2 and 9 (MMP2/9); in vivo, parthenolide inhibits tumor growth and metastasis. Parthenolide has being shown to have agonistic activity against adiponectin receptor 2. Parthenolide is in phase I clinical trials by Ashbury Biologicals for the treatment of cancer. However, there is no recent report of this research.

δ-Tocopherol (δ-T) is a chiral organic molecule belonging to the group of tocopherol, that vary in their degree of methylation of the phenol moiety of the chromanol ring. It was revealed, that δ-Tocopherol had a more potent anticancer activity in solid tumors compared to the other tocopherols, δ-T possessed antileukemic activity of in acute myeloid leukemia (AML). δ-T induced tumor cell death through peroxisome proliferator-activated receptor γ (PPAR-γ) induction, cyclin-D1 inhibition, and modulation of redox balance. In addition, on animal models was found, that δ-tocopherol was more active than α- or γ-tocopherol in inhibiting lung tumor growth, possibly through trapping reactive oxygen and nitrogen species and inducing apoptosis.