PF-04217903 is a triazolopyrazine inhibitor of c-MET that displays anticancer chemotherapeutic and anti-metastatic activities. PF-04217903 inhibits cell proliferation, invasion, and migration as well as tumor growth in various cancer models. In animal models of pancreatic neuroendocrine tumors, this compound prevents lymph node metastasis. PF-04217903 had been in phase I clinical trials by Pfizer for the treatment of solid tumors. In 2011, the company discontinued the development of the compound.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Ilorasertib (previously known as ABT-348), an orally bioavailable ATP-competitive inhibitor of Aurora kinases (A, B and C), as well as the VEGF and PDGF families of receptor tyrosine kinases, was developed by AbbVie as an antineoplastic agent. It is known that Aurora kinases A, B, and C play essential roles in mitotic checkpoint control and are overexpressed by a wide variety of tumor cell types. Both VEGFRs and PDGFRs may be upregulated in various tumor cell types. Ilorasertib alone or in combination with azacitidine demonstrated activity in preclinical models in various hematological malignancies, indicating that pan-Aurora kinase and multiple kinase inhibition may have preferential antileukemic activity. Ilorasertib participated in phase I clinical for patients with advanced hematologic malignancies. The result has shown that the drug could be further studied in acute myelogenous leukemia. Ilorasertib is also going to be studied in phase II clinical trials to learn if this drug can help to control CDKN2A-deficient cancer in patients with advanced cancers.

I-BET-762 (GSK 525762) is a small molecule benzodiazepine, by 'mimicking' acetylated histones interferes with the recognition of acetylated histones by BET family of bromodomains (BRD2, BRD3, and BRD4), which disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumour cell growth. GlaxoSmithKline is developing GSK 525762 for the oral treatment of solid tumours and haematological malignancies.

Defactinib is an oral, investigational drug candidate for the treatment of various solid tumors. Through dual inhibition of FAK and PYK2, defactinib targets key resistance mechanisms in the tumor microenvironment (TME), including limited local immune response, dense stroma, and resident cancer stem cells, that may limit the effectiveness of current and investigational treatments. Treatment-related adverse events are: unconjugated hyperbilirubinemia, fatigue and headache.

T-900607 is a pentafluorophenylsulphonamide derivative patented by Tularik Inc. as antiproliferative agent. Antitumor mechanism of T900607 is similar to the vinca alkaloids in terms of disruption of microtubule polymerization but uniquely causes a specific covalent modification of β-tubulin. In preclinical studies, T900607 was shown to bind irreversibly and specifically to the β1, β2, and β4 isotypes of β-tubulin is not a substrate for p-glycoprotein drug pump and has activity in the preclinical setting in MDR models. T900607 was evaluated in human tumor xenografts and showed activity in MX-1, MCF-7, and MCF-7/ADR mammary, C13 ovarian, HT 29 colon, and Caki-1 renal carcinoma as well as lymphoblastic leukemia, with equal or more efficacious effects compared to vinblastine, doxorubicin and paclitaxel. In a clinical trial, T-900607 shows significant toxicity, consisting of thrombocytopenia, nausea/vomiting, fatigue, and apparent cardiac toxicity.

LY-3009120 is an orally available inhibitor of all members of the serine/threonine protein kinase Raf family, including A-Raf, B-Raf, and C-Raf protein kinases, with potential antineoplastic activity. Upon administration, pan-RAF kinase inhibitor LY3009120 inhibits Raf-mediated signal transduction pathways, which may inhibit tumor cell growth. Raf protein kinases play a key role in the RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, which is often dysregulated in human cancers and plays a key role in tumor cell proliferation and survival. LY3009120 is being investigated in phase I clinical trial.

Pyrazoloacridine is a pyrazolo[3,4,5-kl]acridine derivative patented by Warner-Lambert Co. as an anticancer agent. Pyrazoloacridine acts as topoisomerase I and II inhibitor that decrease the formation of topoisomerase-DNA adducts. In vitro experiments, Pyrazoloacridine shows efficacy against multidrug-resistant neuroblastoma doxorubicin-resistant human colon carcinoma and breast cancer cell lines. In clinical trials, Pyrazoloacridine demonstrates moderate efficacy in metastatic breast cancer and a high level of adverse events. The dose-limiting toxicity was grade 4 neutropenia. Other grade 3 and 4 toxicities include vomiting, nausea, neurotoxicity, fatigue, and anemia.

Oxi0-4503 (now known as combretastatin A1 phosphate), a diphosphate prodrug of combretastatin A1, was developed by Mateon therapeutics as a second-generation, dual-mechanism vascular disrupting agent from the combretastatin family. On November 21, 2012, Oxi-4503 has been granted orphan designation by the US Food and Drug Administration for the treatment of acute myelogenous leukemia. It is known that the orphan drug designation qualifies a company for several benefits, including the potential for market exclusivity, development grants, and tax credits. Oxi0-4503 is currently participating in phase I/II clinical trial the treatment of patients with acute myelogenous leukemia or myelodysplastic syndrome. In addition, phase I clinical trial was successfully completed where was studied the safety of Oxi0-4503 in patients with advanced solid tumors.