Dacarbazine (DTIC), also known as imidazole carboxamide, is an antineoplastic agent, which is used in the treatment of metastatic malignant melanoma. In addition, this drug also is indicated for Hodgkin’s disease as a second-line therapy when used in combination with other effective agents. Dacarbazine works by methylating guanine at the O-6 and N-7 positions. Guanine is one of the four nucleotides that makes up DNA. The alkylated DNA strands stick together such that cell division becomes impossible. This affects cancer cells more than healthy cells because cancer cells divide faster. Dacarbazine is bioactivated in liver by demethylation to "MTIC" and then to diazomethane, which is an alkylating agent. Symptoms of anorexia, nausea, and vomiting are the most frequently noted of all toxic reactions. Over 90% of patients are affected with the initial few doses.

Cemadotin (LU103793) is a cytotoxic water-soluble pentapeptide analogue of dolastatin 15. The dolastatin peptides were originally isolated from the shell-less mollusc Dolabella auricularia. Cemadotin blocks cells at mitosis. It exerts its antitumor activity by suppressing spindle microtubule dynamics through a distinct molecular mechanism by binding at a novel site in tubulin. Cemadotin was in phase II clinical trials as a promising cancer chemotherapeutic agent. However, this agent appears to be inactive in the treatment of advanced non-small-cell lung cancer and other tumors and this research has been discontinued.

Pivanex, also known as AN-9, is a histone deacetylase inhibitor analog of butyric acid that causes apoptosis of cancer cells through signaling cellular differentiation. AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression, and HIF-1a. An important property of the AN-9 as anticancer agents is its ability to inhibit the growth of multidrug-resistant cancer cells including MCF- 7 Dx, HL-60Mx, and MES-SA-DX and to interact in synergy with doxorubicin in killing cancer cells. Combination of AN-9 and radiation significantly increased mortality of glioma cell lines and, in vivo, inhibited tumor growth and prolonged time to failure in mice bearing glioma xenografts, demonstrating their radiosensitizing function. In clinical trials. Pivanex is well tolerated in patients with advanced NSCLC and is indicative of anti-cancer activity.

Exherin is a small, cyclic pentapeptide vascular-targeting agent with potential antineoplastic and antiangiogenic activities. ADH-1 selectively and competitively binds to and blocks N-cadherin, which may result in disruption of tumor vasculature, inhibition of tumor cell growth, and the induction of tumor cell and endothelial cell apoptosis. In murine melanoma xenografts, ADH-1 in combination with melphalan significantly reduced tumor growth up to 30-fold over melphalan alone. ADH-1 enhancement of response to melphalan was associated with increased formation of DNA adducts, increased apoptosis, and intracellular signaling changes. In a pilot study (phase I trial), ADH-1 intravenous pretreatment before chemotherapy in metastatic melanoma completely destroyed tumors in half of patients

P276-00 (also known as riviciclib) is a novel, potent, small-molecule, flavone-derived inhibitor of cyclin-dependent kinases (Cdk), Cdk 4 D1, Cdk1 B, and Cdk9 T, with potent cytotoxic effects against chemosensitive and chemoresistant cancer cell lines. P276-00 was in phase II clinical trial for the treatment mantle cell lymphoma, but that study was terminated based on interim results and all subjects were off study at that time. Although, there were not the major safety or tolerability concerns. However, this drug successfully passed phase II clinical trial for the treatment Melanoma, squamous cell carcinoma of head and neck, malignant melanoma and in combination with Gemcitabine in the treatment of advanced pancreatic cancer.

Arctigenin is a plant lignan extracted from Arctium lappa that has been shown to have estrogenic properties. In ER-positive MCF-7 cells, arctigenin efficiently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell migration and invasion. Arctigenin confers anti-metastatic effects by inhibiting MMP-9 and uPA via the Akt, NF-κB and MAPK signaling pathways on breast cancer, regardless of ER expression. Intake of arctigenin could be an effective supplement for breast cancer patients. Arctigenin is a phenylpropanoid dibenzylbutyrolactone lignan compound possessing antitumor, anti-inflammatory, anti-influenza, antioxidant, antibacterial, and hypoglycaemic activities. Arctigenin exhibited significant antiproliferative activity against CCRF-CEM cells after 72 h treatment with IC50 values of 1.21 ± 0.15 um. It arrested CCRF-CEM cells in the S phase. It induced apoptosis in CCRF-CEM cells in a concentration- and time-dependent manner. Arctigenin is a good candidate for the development of novel agents against T-cell lymphoma. Arctigenin has been found to act as an agonist of adiponectin receptor 1 (AdipoR1). Arctigenin is an antagonist of MR and effectively decreases the Na/K-ATPase 1 gene expression, thus highlighting its potential as an anti-hypertensive drug lead compound.

Imexon (INN, trade name Amplimexon) is a substance that is being studied in the treatment of some types of cancer, including pancreatic, lung, breast, prostate, melanoma, and multiple myeloma. Imexon is a thiol-binding small molecule which induces mitochondrial oxidation, a loss of membrane potential and cytochrome C, leading to apoptosis.

Betulinic acid (BA) is a plant-derived pentacyclic triterpenoid that exerts potent anti-cancer effects in vitro and in vivo. It`s anticancer property is linked to its ability to induce apoptotic cell death in cancer cells by triggering the mitochondrial pathway of apoptosis. In contrast to the cytotoxicity of betulinic acid against a variety of cancer types, normal cells and tissue are relatively resistant to betulinic acid, pointing to a therapeutic window. Compounds that exert a direct action on mitochondria present promising experimental cancer therapeutics, since they may trigger cell death under circumstances in which standard chemotherapeutics fail. Thus, mitochondrion-targeted agents such as betulinic acid hold great promise as a novel therapeutic strategy in the treatment of human cancers. Betulinic acid has antiretroviral, antimalarial, and anti-inflammatory properties. Betulinic acid exerts its inhibitory effect by preventing topoisomerase I-DNA interaction as a result of which the 'cleavable complex' is not formed. In consequence, it also acts as an antagonist to camptothecin-mediated cleavage. The antitumor pharmacological effects of BA consist of triggering apoptosis via the mitochondrial pathway, regulating the cell cycle and the angiogenic pathway via factors, including specificity protein transcription factors, cyclin D1 and epidermal growth factor receptor, inhibiting the signal transducer and activator of transcription 3 and nuclear factor‑κB signaling pathways, preventing the invasion and metastasis of tumor cells, and affecting the expression of topoisomerase I, p53 and lamin B1. Betulinic Acid has also been used in trials studying the treatment of Dysplastic Nevus Syndrome. Betulinic acid acts as anti-melanoma agent through inhibiting aminopeptidase N activity with IC50 of 7.3 uM. Betulinic acid is an inhibitor of HIV-1 with EC50 of 1.4 uM.

Pyrazofurin (PF) (3,β-D-ribofuranosyl, 4-hydroxyprazole-5-carboxamide) is a C-nucleoside antibiotic, one in which the ribose joins the base-ring carbon instead of a base-ring nitrogen. Pyrazofurin potently inhibits orotidine 5'-monophosphate (OMP) decarboxylase, thereby interfering with de novo synthesis of uridine nucleotides and resulting in cytotoxicity. This agent also causes a rapid depletion of the pyrimidine deoxynucleotide pool, thereby inhibiting DNA synthesis and cell replication. PF was isolated from fermentation filtrate of Strepomyces candidus. This compound was initially found to have inhibitory activity against the vaccinia, herpes simplex, rhino and measles viruses in vitro and the vaccinia virus in vivo. More recently the antiviral spectrum has been extended to include the polio, Coxsackie, Sindbis and vesicular stomatitis viruses.

Solamargine is the one of major compounds of Solanum lycocarpum- fruit glycoalkaloid extract, and a major steroidal alkaloid glycoside, which is purified from Solanum nigrum L (SNL), a traditional Chinese medicinal herb. It has been shown that solamargine has anti-tumor activity against the several types of cancers. Also as a part of SR-T100 Gel solamargine in the phase II of clinical trial for the treatment of Actinic Keratosis and Bowen's Disease. The precise mechanism of its actions is still undefined, but existed several potential pathways. In case of castration-resistant prostate cancer cells, solamargine inhibits the growth cells through AMPKalpha-mediated inhibition of p65, followed by reduction of MUC1 expression in vitro and in vivo. In case of lung cancer cells solamargine inhibits the growth cells through reduction of EP4 protein expression, followed by increasing ERK1/2 phosphorylation. The inter-correlations between EP4, DNA methyltransferase 1 (DNMT1) and c-Jun and feedback regulation of ERK1/2 by c-Jun contribute to the overall responses of solamargine in this process.