Naltrindole is a highly potent, highly selective delta opioid receptor antagonist. It is predominantly used as a molecular probe in biomedical studies exploring the manipulation of delta opioid receptors. Naltrindole was shown to inhibit cancer cell growth in vitro; potentially through a nonopioid receptor-dependant mechanism.

Gamabufotalin belongs to bufadienolides was first isolated from B. formosus Boulenger and described by Kotake in 1928. Gamabufotalin is a component of traditional Chinese medicinal preparations containing ChanSu, also known as toad venom, a dried product of the skin and parotid venom glands from the Asiatic toad (Bufo gargarizans). Gamabufotalin inhibits sodium/potassium-transporting ATPase activity and exhibited positive inotropic action in the papillary muscle preparations. Gamabufotalin demonstrates significant anti-tumor activity in vitro on cancer cells and in vivo on mouse tumor xenografts. Gamabufotalin, a major derivative of bufadienolide, inhibits VEGF-induced angiogenesis.

Elaiophylin (also known as Azalomycin-B) is a natural compound, a macrolide antibiotic that was first isolated from a culture of Streptomyces melanosporus. Elaiophylin is a novel and potent inhibitor of late-stage autophagy with outstanding antitumor activity in human ovarian cancer cells. In addition was shown, that elaiophylin could be a promising therapeutic strategy for overcoming incurable multiple myeloma (MM), even when TP53 mutations are present. It is known, that autophagy inhibition is a promising approach and is being investigated as a new target strategy for ovarian cancer treatment. Autophagy, a lysosome-dependent pathway, is a complex catabolic process that involves the degradation of dysfunctional or useless cytoplasmic constituents. Thus, elaiophylin, a novel autophagy inhibitor with unique chemical structure, provides the potential for structure-based development of autophagy inhibitors for new cancer therapies. Also, elaiophylin is an inhibitor of a testosterone 5 alpha-reductase.

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.

Piericidin A (also named piericidin A1 in some references) was reported as a new insecticidal metabolite, produced by cultures of the soil-derived actinomycete Streptomyces mobaraensis. Piericidin A resembles coenzyme Q in its overall structure containing a pyridine ring with two adjacent methoxy groups. The most widely recognized biological target of Piericidin A is the mitochondrial electron transport chain protein NADH-ubiquinone reductase (Complex I). Respiratory inhibition by piericidin A can be reversed by the addition of vitamin-K3 (menadione) to the inhibited respiratory chain in mammalian mitochondria. Piericidin A increases ROS production. Piericidin A showed significant cytotoxic activities against several tumor cells, such as mouse leukemia cell line, human colon carcinoma cells and was selectively cytotoxic toward human multiple myeloma cells. Moreover, it was identified as a highly selective antitumor agent with greater selectivity and potency than the comparison standard mitomycin C. Piericidin A aggravates the course of genetically determined tau pathology.

Brucine is an alkaloid resembling strychnine but it is much less potent than strychnine. Brucine was first discovered in 1819 by Pelletier and Caventou in the bark of the Strychnos nux vomica tree. Brucine causes paralysis of the peripheral nerve endings and produces violent convulsions. Since brucine is a large chiral molecule, it has been used as an enantioselective recognition agent using in chiral resolution. While brucine has been shown to have good anti-tumor effects, on both hepatocellular carcinoma and breast cancer, its narrow therapeutic window has limited its use as a treatment for cancer. Brucine is also used in traditional Chinese medicine as an anti-inflammatory and analgesic agent, as well as in some Ayurveda and homeopathy drugs. Like strychnine, brucine also functions as antagonist at the glycine receptor and paralyzes the inhibitory neurons

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.

Panobinostat is an oral deacetylace (DAC) inhibitor approved on February 23, 2015 by the FDA for the treatment of multiple myeloma. The approval was accelerated based on progression-free survival, therefore confirmatory trials by the sponsor to demonstrate clinical efficacy in multiple myeloma treatment are in progress of being conducted. Panobinostat is marketed by Novartis under the brand name Farydak. Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.

Clofibrate is a fibric acid derivative used to lower cholesterol and triglyceride (fat-like substances) levels in the blood. This may help prevent medical problems caused by such substances clogging the blood vessels. However, this treatment was discontinued in 2002 due to adverse effects. Clofibrate is an agonist of the PPAR-α receptor in muscle, liver, and other tissues. This agonism ultimately leads to modification in gene expression resulting in increased beta-oxidation, decreased triglyceride secretion, increased HDL, and increased lipoprotein lipase activity. Clofibrate increased the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis, inhibited the synthesis, and increases the clearance of apolipoprotein B, a carrier molecule for VLDL. In addition, clofibrate was investigated as a novel therapy agent in multiple myeloma and it shown the promising results.

Cinchonine is cinchona bark alkaloid, which was used to treat malaria. Cinchonine is more efficient than quinine in increasing the intracellular accumulation and restoring the cytotoxicity of doxorubicin, mitoxantrone and vincristine on well-characterized multidrug resistance (MDR) cell lines. In the phase I of clinical trial was investigated the properties of cinchonine combined with the CHVP (cyclophosphamide, doxorubicin, vinblastine, methylprednisolone) regimen in relapsed and refractory lymphoproliferative syndromes.