Dinaline represents a group of pharmacologically active lipophilic substances with a relatively simple structure derived from N-acyl-o-phenylenediamine. It has been found to exhibit high antineoplastic activity in a series of slowly growing tumors such as chemically induced rat mammary and colorectal carcinomas, osteosarcoma C22LR and Brown Norway myeloid leukemia. The drug was inactive against many of the typically hypersensitive signal tumors, i.e. mouse leukemias P388 and L1210, sarcoma 180 and Yoshida sarcoma. Colon carcinoma cells exposed to dinaline demonstrate distinct but reversible changes in amino acid transport, protein metabolism, DNA synthesis and cell proliferation.

Mivotilate is an orally active hepatoprotective agent for the treatment of liver cirrhosis and hepatitis-B infection. Mivotilate was shown to exert multiple effects on the hepatic cytochrome P450 system, particularly to inhibit CYP2E1 expression and to up-regulate the CYP1A1 expression. The low oral bioavailability of Mivotilate in rats could be primarily attributed to poor absorption and considerable hepatic and gastrointestinal first-pass effects. The thermal reversible microemulsion system of YH439 greatly enhances the bioavailability of YH439 after oral administration. Mivotilate prevents mutagenesis caused by agents such as benzopyrene and reduces skin tumours induced by these agents.

GDC-0152 binds to the XIAP BIR3 domain, the BIR domain of ML-IAP, and the BIR3 domains of cIAP1 and cIAP2. GDC-0152 promotes degradation of cIAP1, induce activation of caspase-3/7, and lead to decreased viability of breast cancer cells. GDC-0152 improves outcome in breast cancer and glioma xenografted mouse. GDC 0512 was in phase I development in the US for the treatment of cancer; however, Roche announced in their 2009 results presentation, that development of the agent has been discontinued.

Declopramide is an apoptosis inducer. Also, it inhibits NFkappaB activation by inhibition of IkappaBbeta breakdown. In preclinical research, Declopramide demonstrated strong antitumor properties. It had been in phase II clinical trials for the treatment of colorectal cancer. However, this research has been discontinued.

Fialuridine I-124 is an isotope-labeled form of fialuridine, or 1-(2-deoxy-2-fluoro-1-D-arabinofuranosyl)-5-iodouracil (FIAU), a thymidine nucleoside analog with activity against various herpesviruses and hepatitis B virus (HBV) in vitro and in vivo. Bacterial or herpes virus thymidine kinase (TK) considered to be a target of FIAU. Fialuridine I-124 is a positron emission tomography/computed tomography (PET/CT) tracer that was developed for imaging of cells transfected with the herpes simplex virus 1 (HSV1) thymidine kinase reporter gene. This enzyme transfers a γ phosphate group fom ATP to the 5’ hydroxyl group of pyrimidine deoxynucleosides. The lipophilic tracer diffuses into the cell and is trapped in the cell with HSV1-TK activity, because the phosphorylated tracer cannot pass the plasma membrane. TK gene of bacteria was sufficiently similar to that of the viral TK of HSV1 and fialuridine I-124 could also be phosphorylated by the endogenous bacterial TK. Once phosphorylated by TK, fialuridine I-124 becomes trapped within bacteria and can be detected with positron emission tomography/computed tomography (PET/CT).

Mureletecan is a water-soluble prodrug, consisting of camptothecin covalently linked to polymeric backbone methacryloylglycynamide, with potential antineoplastic activity. After entering tumor cells, the active moiety camptothecin is slowly released from mureletecan via hydrolysis of the ester linkage. Camptothecin, the active moiety, is an alkaloid isolatable from the Chinese tree Camptotheca acuminata. Camptothecin itself suffers from poor solubility, which is why it is often investigated with a solubilizing conjugate; such as in Mureletecan. Camptothecin binds to and stabilizes the topoisomerase I-DNA covalent complex producing potentially lethal double-stranded DNA breaks when encountered by DNA replication machinery. Camptothecin has also been shown to inhibit HIF1a. Camptothecin has been investigated with a number of solubilizing conjugates as a potential treatment in various forms of cancer.

Safingol, the synthetic L-threo-stereoisomer of endogenous (D-erythro-) sphinganine, is an inhibitor of protein kinase C and sphingosine kinase in vitro, and in some cell types has been implicated in ceramide generation and induction of apoptosis. Safingol inhibits enzymatic activity and 3H-phorbol dibutyrate binding of purified rat brain PKC (IC50 = 37.5 uM and 31uM, respectively). Inhibits human PKCα, the major overexpressed isoenzyme in MCF-7 DOXR cells (IC50 = 40 uM). Safingol enhances the cytotoxic effect of the chemotherapeutic agent Mitomycin C (MMC) in gastric cancer cells by promoting drug-induced apoptosis. Safingol is an inhibitor of SphK (Sphingosine kinase). Safingol has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo.

Bisdemethoxycurcumin (BDMC) is a minor constituent (approximately 3%) of curcuminoids that has been shown to be more stable than the other two main curcuminoids, that is, curcumin and desmethoxycurcumin. Bisdemethoxycurcumin inhibits the proliferation and survival of several types of tumor cells including colon cancer cells, breast cancer cells, leukemia cells, and glioma cells. In addition, Bisdemethoxycurcumin suppresses cancer invasion and has the highest anti-metastatic potency in HT1080 human fibrosarcoma cells among the three curcuminoids. Bisdemethoxycurcumin has been reported to possess anti-oxidant and anti-inflammatory activities. However, the underlying molecular mechanisms responsible for the inhibitory action of Bisdemethoxycurcumin on tumor invasion and migration have remained largely unknown. More interestingly, the anti-cancer effects of Bisdemethoxycurcumin are comparable to and sometimes more potent than those of curcumin in different conditions.

Tenifatecan (also known as SN2310 or tocopherol succinate-SN38), camptothecin, is an injectable emulsion composed of vitamin E, a succinate derivative, as well as 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan. It is known that SN-38 binds to and inhibits topoisomerase I by stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis. Tenifatecan successfully completed phase I clinical trial in patients with advanced solid tumors. Achieve Life Sciences, the company that is developing this drug, are currently exploring options to out-license tenifatecan.

Taltobulin, also known as HTI-286 and SPA-110, is a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. Taltobulin was a potent inhibitor of proliferation (mean IC50 = 4 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Taltobulin showed strong antitumor activity both in androgen-dependent and androgen- independent tumors and may be a promising agent in second- line treatment strategies for patients suffering from docetaxel- refractory prostate cancer.