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.

1H-2-BENZOPYRAN-3-ACETIC ACID, 8-HYDROXY-6-METHOXY-Α-METHYL-1-OXO- (NM-3) is an orally bioavailable antiangiogenic isocoumarin with potential antineoplastic activity. NM-3 inhibits vascular endothelial growth factor (VEGF), a pro-angiogenic growth factor, thereby inhibiting endothelial cell proliferation. NM-3 induces apoptosis by a mechanism involving reactive oxygen species. In human MCF-7 and ZR-75-1 breast cancer cells, NM-3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G1-S-phase, and necrotic cell death. NM-3 has been used in trials studying the treatment of solid tumours.

Flumatinib (HHGV678) is an orally bioavailable antineoplastic tyrosine kinase inhibitor. Flumatinib inhibits the wild-type forms of Bcr-Abl, platelet-derived growth factor receptor (PDGFR) and mast/stem cell growth factor receptor (SCFR; c-Kit) and forms of these proteins with certain point mutations. Flumatinib was extensively metabolized after oral administration, and the major metabolic pathways observed were amide hydrolysis, demethylation, oxidation, and glucuronide conjugation. It is in phase III clinical trials for the treatment of Chronic myeloid leukemia (in China).

Iincyclinide, also known as CMT-3 and COL-3, is an MMP inhibitor and a chemically-modified tetracycline with potential antineoplastic activity patented by Chas. Pfizer & Co. Incyclinide has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture. Incyclinide is an especially effective inhibitor of the growth and viability of filamentous fungi. Unfortunately, in clinical trials, Iincyclinide failed to demonstrate efficacy in Lymphoma, Melanoma, Renal Cell Carcinoma, and some other tumors.

Licochalcone A (LicA) is a flavonoid isolated from the famous Chinese medicinal herb Glycyrrhiza uralensis Fisch and has a wide spectrum of pharmacological activities such as anti-oxidant, anti-bacterial, anti-viral, and anti-cancer. However, its pharmacological mechanism is not well defined. The anti-Inflammatory effects of LicA on IL-1β-Stimulated human osteoarthritis chondrocytes was reached by activating Nrf2 signaling pathway. LicA showed anti-proliferative and apoptotic effects in breast cancer cells through regulating Sp1 and apoptosis-related proteins in a dose- and a time-dependent manner. In addition, the chemotherapeutic potential of LicA for treatment of human cervical cancer was achieved by inhibition of PI3K/Akt/mTOR signaling.

Lucitanib (E-3810) is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. A Phase I/IIa clinical trial of lucitanib was initiated in 2010 and has demonstrated multiple objective responses in FGFR1 gene-amplified breast cancer patients, and objective responses were also observed in patients with tumors often sensitive to VEGFR inhibitors, such as renal cell and thyroid cancer. Lucitanib is an oral, potent inhibitor of the tyrosine kinase activity of fibroblast growth factor receptors 1 through 3 (FGFR1-3), vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3) and platelet-derived growth factor receptors alpha and beta (PDGFR alpha-beta). The most common adverse events were hypertension, asthenia, and proteinuria.

S 3304 is a potent, orally active, noncytotoxic inhibitor of matrix metalloproteinases, primarily MMP-2 and MMP-9 that was developed by Shionogi as an anticancer agent. This drug has prolongs survival in mice xenografts and was well tolerated in healthy volunteers. S 3304 had completed phase I clinical trials for patients with locally advanced non-small cell lung cancer and with advanced solid tumors, however, the company had discontinued the further development of S 3304.

GPX-150 is an anthracycline compound that is being tested for treatment in patients with soft-tissue sarcomas. This doxorubicin (DOX) analog does not show the cumulative dose-dependent cardiotoxicity of DOX. It works by reducing the formation of reactive oxygen species and the cardiotoxic metabolite, doxorubiciniol, the two pathways that are linked to the irreversible cardiotoxicity seen with DOX. Phase 1 clinical trials showed no irreversible, cumulative dose-dependent cardiotoxicity. A phase 2 study investigating the safety and efficacy of GPX-150 in patients with soft tissue sarcoma has been completed. No patients developed any evidence of irreversible, cumulative dose-dependent chronic cardiotoxicity. Toxicities reported include grade 3 anemia, neutropenia, and grade 4 leukopenia.

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