3,3',5,5'-Tetraiodothyroacetic acid (Tetrac) is a deaminated analog of L-thyroxine (T4) that blocks the proangiogenesis actions of T4 and 3, 5, 3’-triiodo-L-thyronine as well as other growth factors at the cell surface receptor for thyroid hormone on integrin αvβ3. 3,3',5,5'-Tetraiodothyroacetic acid blocks the transcriptional activities directed by L-thyroxine (T4) and 3,5,3’-triiodo-L-thyronine (T3) at αvβ3, but, independently of T4 and T3, 3,3',5,5'-Tetraiodothyroacetic acid modulates transcription of cancer cell genes that are important to cell survival pathways, control of the cell cycle, angiogenesis (VEGFA, FGF), apoptosis, cell export of chemotherapeutic agents, and repair of double-strand DNA breaks. 3,3',5,5'-Tetraiodothyroacetic acid was found to perturb the angiogenesis process stimulated by VEGF (Vascular Endothelial Growth Factor) or FGF (Fibroblast Growth Factor) without influencing the preexisting blood vessels.

Ergosterol endoperoxide is a derivative of ergosterol. It has been isolated from a variety of fungi, yeast, lichens and sponges. Ergosterol endoperoxide has been shown to inhibit the growth of some cancer cells and to induce apoptosis of HL60 human leukemia cells. Ergosterol endoperoxide also decreases lipid peroxidation of rat liver microsomes and suppresses the proliferation of mouse and human lymphocytes stimulated with mitogens. It has been reported as having immunosuppressive, antiplasmodial, antimycobacterial, antiviral, anti-inflammatory and antitumoural properties. The interaction of Trypanosoma cruzi with ergosterol peroxide in vitro resulted in a strong lytic activity possibly due to the disruption of the parasite membrane.

DMH1 is a potent and selective inhibitor of BMP signaling. DMH1 is a direct inhibitor of ALK2 BMP type-I receptor ALK2 (activin receptor like kinase-2). DMH1 potently inhibits neoplastic phenotype in cancer cells.

AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

RKI 1447 is a potent and selective ROCK inhibitor. It displays anti-invasive and antitumor activities in breast cancer cells. RKI-1447 can inhibit the proliferation, migration and invasion abilities of ovarian cancer cells. RKI 1447 exhibits cytotoxic and cytostatic effects on VHL-deficient clear cell renal cell carcinoma (CC-RCC), making them candidate novel therapeutics for CC-RCC. RKI-1447 significantly inhibited mammary tumor growth in animal models.

Pteropodine is a heterohimbine-type oxindole alkaloid specifically isolated from ‘Cat’s claw’ (Uncaria tomentosa), a plant that has shown cytostatic, anti-inflammatory and antimutagenic properties and is used in traditional medicine to cure a number of diseases. Pteropodine positively modulate the function of rat muscarinic M1 and 5-HT2 receptors expressed in Xenopus oocyte but further studies are necessary to elucidate the exact mechanism by which Pteropodine positively modulates muscarinic M1 and 5-HT2 receptor functions. Pteropodine reduced the sister-chromatid exchanges and micronucleated polychromatic erythrocytes production by doxorubicin in mouse, showing a protective effect on the in vivo DNA damage. Pteropodine exhibited a significant pro-apoptotic effect on Medullary thyroid carcinoma cells. Moreover, anti-proliferative effect of pteropodine was demonstrated on the acute lymphoblastic leukaemia cells and ovarian carcinoma cells.

CB 300919 is a water-soluble analogue of CB30865. Preclinical data revealed that CB 300919 was a potential therapy for ovarian cancer, what was shown for tumor xenograft mice. CB 300919 is an inhibitor of Nicotinamide phosphoribosyltransferase.

4-Amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (Epacadostat) is an orally available hydroxyamidine and inhibitor of indoleamine 2,3-dioxygenase (IDO1), with potential immunomodulating and antineoplastic activities. epacadostat targets and binds to IDO1, an enzyme responsible for the oxidation of tryptophan into kynurenine. By inhibiting IDO1 and decreasing kynurenine in tumor cells, epacadostat increases and restores the proliferation and activation of various immune cells, including dendritic cells (DCs), NK cells, and T-lymphocytes, as well as interferon (IFN) production, and a reduction in tumor-associated regulatory T cells (Tregs). Activation of the immune system, which is suppressed in many cancers, may inhibit the growth of IDO1-expressing tumor cells. IDO1 is overexpressed by a variety of tumor cell types and DCs. Epacadostat is in clinical development as a novel orally active immuno-oncological therapy.

GSK1070916 is a novel, azaindole derived, reversible and ATP-competitive inhibitor of the Aurora B/C kinases. GSK1070916 inhibits the proliferation of tumor cells and has antitumor effects in 10 human tumor xenograft models including breast, colon, lung, and two leukemia models. Nemucore Medical Innovations and Cancer Research UK are developing NMI 900 (previously GSK 1070916) for the intravenous treatment of cancer. The product was originally developed by GlaxoSmithKline. A phase I/II trial in patients with solid tumours has been completed in the UK. Phase II development in ovarian cancer is underway in the US.

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.