Indotecan (LMP400) is a novel indenoisoquinoline derivative with specific topoisomerase I inhibition activity, developed by Division of Cancer Treatment and Diagnosis National Cancer Institute for cancer treatment. In preclinical studied Indotecan inhibited the cell growth of established mouse pheochromocytoma cell lines and primary human tumor tissue cultures. Low doses of Indotecan decreased the protein levels of hypoxia-inducible factor 1 (HIF-1α), one of a family of factors studied as potential metastatic drivers in these tumors. In vitro, Indotecan showed an increase in the growth-inhibitory effects in combination with other chemotherapeutic drugs that are currently used for the treatment of pheochromocytoma. Recently Indotecan has entered Phase I clinical trials for the treatment of cancer patients at the National Cancer Institute, and definite plans are being formulated to commence Phase II clinical trials.

BMS-863233, also known as XL413, is a potent and selective cell division cycle 7 (CDC7) kinase inhibitor with potential antineoplastic activity. BMS-863233 binds to and inhibits the activity of CDC7, which may result in the inhibition of DNA replication and mitosis, the induction of tumor cell apoptosis, and the inhibition of tumor cell proliferation in CDC7-overexpressing tumor cells. CDC7, a serine-threonine kinase overexpressed in a variety of tumor cell types, plays an essential role in the initiation of DNA replication by activating origins of replication.

Teglarinad (also known as GMX1777) is a prodrug of GMX1778 and is an inhibitor of nicotinamide phosphoribosyl transferase (NAMPT). It is known that NAMPT involves in NAD(+) biosynthesis, which serves as an important substrate for proteins involved in DNA repair. Teglarinad was evaluated in two human head and neck cancer models in combination with radiotherapy. It was shown that the combining GMX1777 with pemetrexed was an effective new therapeutic strategy to treat nonsquamous non-small cell lung carcinoma (NSCLC). In addition, the drug participated in clinical trial phase I/II in combination with temozolomide for the treatment of metastatic melanoma, however, this study was terminated due to financial constraints.

Indimitecan, also known as LMP776, is a novel topoisomerase I inhibitor. A substance being studied in the treatment of cancer. It blocks certain enzymes that break and rejoin DNA strands. These enzymes are needed for cells to divide and grow. Blocking them may cause cancer cells to die. Indimitecan (LMP776) also helps anticancer drugs kill cancers that are resistant to some other drugs. LMP776 is a type of indenoisoquinoline and a type of topoisomerase inhibitor. In vitro, LMP776 induces TOP 1 cleavage at unique genomic positions and causes cell cycle arrest in both S and G (2)-M phases. Protein linked DNA breaks were observed in cells treated with nanomolar concentrations of LMP776.

MP-412 (AV-412) is a potent dual inhibitor of EGFR and ErbB2 tyrosine kinases, including the mutant EGFR (L858R,T790M), which is clinically resistant to the EGFR-specific kinase inhibitors erlotinib and gefitinib. AV-412 has potential as a therapeutic agent for the treatment of cancers expressing EGFR and ErbB2, especially those resistant to the first generation of small-molecule inhibitors.AVEO Pharmaceuticals was developing AV-412 for the treatment of cancer, however development has been discontinued.

Millennium (a wholly-owned subsidiary of Takeda) was developing TAK- 901 for the treatment of cancer. TAK-901 is an inhibitor of Aurora A/B with IC50 of 21 nM/15 nM. It is not a potent inhibitor of cellular JAK2, c-Src or Abl. TAK-901 is in phase I clinical trials by Millennium Pharmaceuticals for the treatment of advanced hematological malignancies. TAK-901 had been in phase I clinical trials for solid tumors. However, this study was discontinued.

Imiloxan is a highly selective alpha2B adrenoceptor antagonist and was developed for depression in the 1980s. In Phase 1 clinical trials imiloxan dosing led to hypersensitivity reactions; the molecule's development was discontinued.

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.

Teglarinad (also known as GMX1777) is a prodrug of GMX1778 and is an inhibitor of nicotinamide phosphoribosyl transferase (NAMPT). It is known that NAMPT involves in NAD(+) biosynthesis, which serves as an important substrate for proteins involved in DNA repair. Teglarinad was evaluated in two human head and neck cancer models in combination with radiotherapy. It was shown that the combining GMX1777 with pemetrexed was an effective new therapeutic strategy to treat nonsquamous non-small cell lung carcinoma (NSCLC). In addition, the drug participated in clinical trial phase I/II in combination with temozolomide for the treatment of metastatic melanoma, however, this study was terminated due to financial constraints.

CEP-32496 (RXDX 105) is an orally administered, small molecule, VEGFRsparing, RET, BRAF, EGFR tyrosine kinase inhibitor, for the treatment of solid tumours, including malignant melanoma and colorectal cancer. CEP-32496 was originally discovered by Ambit Biosciences (now Daiichi Sankyo) and Cephalon (now owned by Teva) as part of a research programme to develop orally administered kinase inhibitors. The worldwide rights to the compound were licensed to Teva by Ambit, following the acquisition of Cephalon by Teva. Teva, in March 2015, entered into an asset purchase agreement with Ignyta, pursuant to which, Ignyta has acquired worldwide rights and assets of four oncology development programmes, including CEP-32496. Following the acquisition of the compound by Ignyta, CEP 32496 has been renamed to RXDX 105. Phase I/Ib development of RXDX 105 for the treatment of advanced solid tumours is underway in the US.